I devoted 5 years of my life to Apple Retail. Well, devoted might be too strong of a word. I was "there" though (physically).
My day-to-day involved working "the queue" making sure that everyone with a broken Mac, iPhone, or iPod Nano received my help.
Oh, you moved the hard drive into the trash?
Oh, you spilled Fat Tire all over your keyboard?
Oh, you dropped your Nano Pod in the toilet?
Answers to these questions required little or no use of my brain. However, about every other day or so, I would meet the original-customer-from-hell, requiring significant adaptation for a high-stakes battle of mental chess.
While my coworkers chose to self-medicate in the mall parking lot, I would take various pharmaceuticals, herbs, hormones, and vitamins in hopes of becoming more resilient in these intermittent situations. If something was able to brighten my disposition towards the businessman that dropped his computer in the bathtub and wanted me to replace it for him—for free—then whatever I was doing probably had a measurable effect.
One product I experimented with extensively was pregnenolone. As we discussed in the Becoming Stress Proof Email Series, pregnenolone is produced from active thyroid hormone (triiodothyronine, or T3), vitamin A, and low-density lipoprotein, or LDL in the energy apparatus of the cell, the mitochondria.
Used in the first stage of hormone synthesis, the production of youthful, anti-stress hormones depends on its availability.
However, there are some strange ideas floating around in regards to pregnenolone. While I'm not exactly sure where it originated, you will not find the concept in "the scientific literature," nor will your physician be able keep a straight face if you suggest it as a cause of illness.
Naturopath Sayz I Got The Pregnenolone Steal
To understand the line of thinking that inspired "pregnenolone steal syndrome," we must first view the body as a machine full of gears, leaky buckets, and leather strap pulleys.
Without doing so, "pregnenolone steal syndrome" makes no fucking sense.
Those that advocate the existence of this phenomenon explain that pregnenolone can either be used in the "DHEA pathway" to produce estrogen and testosterone, or the "progesterone pathway" to produce aldosterone and cortisol.
It is said that during stress pregnenolone is "shunted" towards the "progesterone pathway" increasing production of cortisol, and overtime, leaving deficiencies in progesterone, DHEA, testosterone, aldosterone, and estrogen.
Estrogen Deficiency: Evidence For Pregnenolone Steal?
At first glance "pregnenolone steal," in a faulty context, makes a lot of sense, especially when coupled with the pharmaceutical doctrine that is "estrogen deficiency."
For example, if a young woman stops menstruating, she must have a problem with estrogen, because everyone knows that estrogen is "the female hormone." "Pregnenolone steal syndrome" allows for an easy (understandable) mechanic-like explanation.
When exploring the history and function of estrogen, however, the idea is absurd.
Hans Selye, a pioneer in estrogen research, rejected the idea that estrogen was "the female hormone," and demonstrated that estrogen didn't produce estrus (why it was named) unless simultaneous progesterone was given.
Selye called estrogen "adipin," to more closely align with its production in the fat tissue, but also referred to it as "folliculin" because of the ovarian follicle's significant role in its production.
Far from being "the female hormone" Selye's research focused on estrogen's ability to mimic the first stage of stress (shock), which included:
- A decrease in the metabolic rate (thyroid inhibition)
- Destruction of the thymus gland ("immunity central")
- The release of free fatty acids as fuel (reduced ability to use glucose)
- Increased utilization of glycogen reserves (an "anti-stress" factor)
- Increased blood lactate (inflammatory)
In addition to estrogen's forgotten role in stress, lab work used to justify "estrogen deficiency" is highly dubious. It has been found that estrogen increases with age and while serum levels can be low, tissue levels can be very high.
Side Note: While taking estrogen can decrease symptoms in some menopausal women, it should be noted that the pituitary gonadotrophins, FSH and LH, which when elevated can cause many problems (they're sometimes called the "menopausal hormones"), can be suppressed with estrogen supplementation. P.W. Wise found that regulatory nerves in the brain responsible for releasing FSH and LH were "desensitized" in relation to their exposure to estrogen.
Pregnenolone In The Real Organism
Like adrenal fatigue, being "diagnosed" with "pregnenolone steal syndrome" casts a totally wack context for achieving wellness.
In the above scenario, taking supplemental pregnenolone could contribute to the over-production of cortisol, while a case could be made for supplementing estrogen.
Outside the context of pharmaceutical physiology, you'll find that hormonal synthesis doesn't work like the pictures and diagrams you find when you type "pregnenolone steal" into Google.
Far from increasing cortisol, supplemental pregnenolone, or simply increasing our own production, inhibits the pituitary's release of ACTH, which signals the adrenal glands to produce cortisol.
Moreover, estrogen stimulates ACTH, increasing cortisol.
When approaching the idea of "optimizing" our own production of pregnenolone, it seems logical to start with where it's produced, the cell.
The Cell: Pregnenolone HQ
In the first step of sugar metabolism, glucose is broken down in a process known as glycolysis, providing two molecules of pyruvate and a small amount of ATP.
Next, pyruvate enters the mitochondria where it is further metabolized by the pyruvate dehydrogenase complex into acetyl-CoA. This process decarboxylates pyruvate, which means that it releases carbon dioxide.
Note: This is especially important, because pyruvate decarboxylation is a step not found in the oxidation of fatty acids and provides a significant amount of carbon dioxide. Among its many functions, carbon dioxide increases the oxygenation of tissues, referred to as the Bohr effect.)
If oxygen is available, and the mitochondria are able to use it (i.e., the absence of Warburg's "respiratory defect"), acetyl-CoA, goes on to produce more carbon dioxide and energy in the Krebs cycle. The whole process is known as mitochondrial respiration (or oxidative metabolism) and is characteristic of a low-stress youthful metabolism.
However, in the presence of increased estrogen, serotonin, unsaturated fats, iron, etc. respiration is inhibited leading to pyruvate being converted into lactic acid. While often referred to as "fuel," in the whole organism, lactic acid:
- causes the cell to take up calcium, which can damage the mitochondria and lead to cell death
- drains the liver of its glycogen (an anti-stress factor) to be converted back into glucose
- opposes and limits the production of carbon dioxide
- excites cells causing them to take up water (edema)
Inhibited respiration leads to a decrease in energy production and a reliance on stress hormones to compensate. This, and not some bogus leaky-bucket-hormonal-cascade syndrome, is relevant if you are unwell.
The ability of the cell to consume oxygen, produce energy, and synthesize anti-stress hormones depends on its high-energy (relaxed) state. Focusing on factors that support respiration: carbon dioxide, thyroid hormone, cholesterol, protein, calcium, magnesium, vitamin A, copper, red light, etc. should allow the body to produce youthful amounts of pregnenolone.
- "Regarding the pregnenolone steal theory, It would be interesting to know who started that, it's a mechanical way of thinking about physiology that ignores the things that really matter. Thyroid hormone, vitamin A, and cholesterol support the formation of pregnenolone, and the well nourished body is able to make large adjustments in these, to minimize the need for cortisol. In health, enough pregnenolone and progesterone are produced to inhibit the stress systems, for example by inhibiting the release of ACTH. When something prevents the formation of pregnenolone and progesterone, rising ACTH will increase its production as conditions permit, but if something, such as thyroid hormone, is lacking, the ACTH will increase cortisol, often with DHEA and the androgens increasing too, if resources permit; sometimes the stressed system is able to sustain only cortisol and aldosterone production, and that leads to degenerative problems." - Ray Peat
- "Analyzing living systems we often have to pull them to pieces, decompose complex biological happenings into single reactions. The smaller and simpler the system we study, the more it will satisfy the rules of physics and chemistry, the more we will 'understand' it, but also the less 'alive' it will be. So when we have broken down living systems to molecules and analyzed their behavior we may kid ourselves into believing that we know what life is, forgetting that molecules have no life at all." - Albert Szent-Györgyi
- “The endocrine organs contribute to the reactions of the organism when an emergency situation arises. This is the case in the event of adrenaline secretion during hypoglycemia or hypotension, or during rage or terror or fear. The role of the endocrine organs in the general-adaptation-syndrome [GAS] of the organism, when confronted with physical or chemical damaging agents or excessive physiological demands, has been brilliantly demonstrated by Selye. According to his studies these reactions, which in principle are generally favorable, can become damaging due to excess or frequent repetition; then they result in pathologic conditions such as nephrosclerosis, arterial hypertension, mycardial lesions, periarteritis, etc.” - Bernardo A. Houssay
- “For the advantage of being able to extract energy from glucose in the absence of oxygen, the anaerobic organism must waste over 90% of the total energy it might be able to obtain if it could oxidize glucose with molecular oxygen to CO2 and H20. In the aerobic organism lactate does not leave the cell; instead it, or pyruvate, is oxidized to CO2 and H20, with the recovery of much of the other 93% of the energy of glucose. Respiration, the oxidation of glucose with molecular oxygen, is clearly very efficient in extracting all of the possible energy from the glucose molecule… Because anaerobic glycolysis can extract only a small fraction of the total energy of the glucose molecule, it is corollary that anaerobic cells must use much more fuel per unit of time per unit of weight to accomplish the same amount of cellular work as an aerobic cell. It has been found that anaerobic cells use up to twenty times as much glucose as aerobic cells to do the same amount of work. And they can consume many times their weight of glucose in only short periods of time.” -Albert Lehninger, PhD (Thanks Rob Turner)
- "Lack of oxygen depresses sugar utilization and—as does any other alarming agent—stimulates the endogenous production of corticoids." - Hans Selye
- Sex steroid hormones in circulatory shock, sepsis syndrome, and septic shock. Fourrier F, et al. METHODS: Estrone (E1), estradiol (E2), testosterone (T), FSH, and LH levels were daily measured during a ten day period in 50 critically ill patients (38 men, 12 post-menopausal women). Patients were separated into four groups: A) no circulatory failure, no sepsis, B) sepsis syndrome without circulatory failure, C) circulatory failure without sepsis syndrome, D) septic shock. Results of hormonal measurements were compared 1) among the 4 groups, 2) between male and female patients, 3) between septic and nonseptic patients. The potential for the infusion of the vasoactive drug dobutamine to induce sex hormonal changes was documented in ten additional septic shock patients by measuring cortisol, E1, and T at base-line and after dobutamine infusion. Changes in active renin and plasma renin activity (PRA) were used as indirect witness of the dobutamine-induced beta 2-stimulation. RESULTS: A dramatic increase in E1 and E2 levels was observed in women of groups B and D, and only in male patients of group D. In the septic patients, estrogen levels peaked at days 1 and 2 and trended to normal from day 6 after the onset of sepsis, while FSH and LH decreased. No difference was found between survivors and non-survivors. Whatever the group, male patients had low T levels throughout the study. Dobutamine induced a significant increase in active renin levels and a decrease in the regression slope between renin and PRA. Cortisol levels remained normal. No significant change in E1 and T was observed after dobutamine. CONCLUSIONS: High estrogen levels were specifically observed in patients with sepsis and septic shock, either males or females. Decreased LH and FSH levels were consistent with the negative feed-back effect of high estrogen levels on pituitary secretion. Circulating T levels were decreased in all male patients. We found no correlation between sequential estrogen levels and outcome. These levels were not modified by a dobutamine-induced beta-2 stimulation. (Thanks Rob Turner)
- Not the "female hormone," but the shock hormone - Ray Peat, PhD
- Menopause and its causes - Ray Peat, PhD
- "Arachidonic Acid’s Role in Stress and Shock" - Rob Turner
- "The chemical machinery of biological oxidation is a rather bulky one. It involves solid state and structure. When the cell divides it has to rearrange its whole interior, which demands mobility. To achieve this the cell has to dispense with its bulky oxidative machinery, dismount it, and revert to the simple and older anaerobic energy production. The faster the cell divides the more completely it will have to revert to fermentation from oxidation as shown by Otto Warburg (1966). Cell divisions and anaerobic fermentation are coupled processes." - Albert Szent-Györgyi
- "Estrogen tends to shift cells away from differentiated functioning and toward simple cell division, a sort of dedifferentiation. This cell division is important for reproduction, and it is also part of a basic process of tissue regeneration. During stress or injury, as well as in normal growth, cell have to make the basic decision of whether to grow or to die in the non-inflammatory process call apoptosis, or to differentiate and contribute to the functional systems of the organism. The heat shock/estrogen system protects cells against "altruistic cell death," but ordinarily the organism rescues the cells from that dedifferentated state by providing energy, oxygen, and signals to restore them to an appropriate functional state." - Ray Peat
- "Estrogens are among the best known of the growth stimulants." - Constance R. Martin
- "This change in perception of menopause can be linked, as it is in many other new “disorders” like erectile dysfunction and irritable bowel syndrome, to a marketing phenomenon by pharmaceutical companies called “if you build it, they will come.” Because pharmaceutical companies have a profound influence on the ways people define and understand diseases, the “if you build it mentality” is often successful in creating a new disease class. After all, pharmaceutical companies have tremendous resources to invent drugs where none existed before, design clinical research to position those drugs in the marketplace, fund patient and professional groups who speak through the popular media, and vigorously promote awareness of their medicines and the ailments they are designed to treat." - Carla Rothenberg - The Rise and Fall of Estrogen Therapy: The History of HRT
- Fertility & Sterility 12(3), 245-260, 1961. "The maintenance of an environment conducive to anaerobic metabolism--which may involve the maintenance of an adequate supply of the substances that permit anaerobiosis...seems to depend primarily upon the action of estrogen." "Glycolytic metabolism gradually increases throughout the proliferative phases of the cycle, reaching a maximum coincident with the ovulation phase, when estrogen is at a peak. Following this, glycolysis decreases, the respiratory mechanisms being more active during the secretory phase. Eschbach and Negelein showed the metabolism of the infantile mouse uterus to be less anaerobic than that of the adult. If estrogen is administered, however, there is a 98 per cent increase in glycolytic mechanisms." "The effect of the progestational steroids may be such as to interfere with the biochemical pattern required for support of this anaerobic environment." M. M. Tikhomirova, et al.
- Clin Endocrinol Metab 1996 Oct;81(10):3639-43 Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic responses to psychosocial stress in healthy young men. "Evidence from animal studies and clinical observations suggest that the activity of the pituitary-adrenal axis is under significant influence of sex steroids. The present study investigated how a short term elevation of estradiol levels affects ACTH, cortisol, norepinephrine, and heart rate responses to mental stress in healthy men. In a double blind study, 16 men received a patch delivering 0.1 mg estradiol/day transdermally, and age- and body mass index-matched control subjects received a placebo patch. Twenty-four to 48 h later, they were exposed to a brief psychosocial stressor (free speech and mental arithmetic in front of an audience). In response to the psychosocial stressor, ACTH, cortisol, norepinephrine, and heart rate were increased in both experimental groups (all P < 0.0001). However, the estradiol-treated subjects showed exaggerated peak ACTH (P < 0.001) and cortisol (P < 0.002) responses compared to the placebo group. Also, the norepinephrine area under the response curve was greater in the estradiol group (P < 0.05). Although heart rate responses differences failed to reach statistical significance, they, too, tended to be larger in the estradiol group. Neither mood ratings before or after the stressor, nor ratings of the perception of the stressor could explain the observed endocrine response differences. In conclusion, short term estradiol administration resulted in hyperresponses of the pituitary-adrenal axis and norepinephrine to psychosocial stress in healthy young men independent of psychological effects, as assessed in this study."
- Mechanisms underlying the resistance of genetic material of the animal cell to stress treatment," Genetika 30(8), 1092-1104, 1994. "...these studies prove that the formation of a mutation is a multistage process involving many cell and organism systems...which are affected by environmental factors.... They can hinder or accelerate the mutational process, in this way providing both a superadditive effect and adaptive response. Recent studies deal with a universal system of heat shock proteins, which is involved in the maintenance of resistance of genetic material and genetic processes in the cell." Gross, "Reproductive cycle biochemistry," Fertility & Sterility 12(3), 245-260, 1961. "The maintenance of an environment conducive to anaerobic metabolism--which may involve the maintenance of an adequate supply of the substances that permit anaerobiosis...seems to depend primarily upon the action of estrogen." "Glycolytic metabolism gradually increases throughout the proliferative phases of the cycle, reaching a maximum coincident with the ovulation phase, when estrogen is at a peak. Following this, glycolysis decreases, the respiratory mechanisms being more active during the secretory phase. Eschbach and Negelein showed the metabolism of the infantile mouse uterus to be less anaerobic than that of the adult. If estrogen is administered, however, there is a 98 per cent increase in glycolytic mechanisms.""The effect of the progestational steroids may be such as to interfere with the biochemical pattern required for support of this anaerobic environment." M. M. Tikhomirova, et al.
- J Clin Endocrinol Metab 1995 Feb;80(2):603-7 The impact of estrogen on adrenal androgen sensitivity and secretion in polycystic ovary syndrome. Ditkoff EC, Fruzzetti F, Chang L, Stancyzk FZ, Lobo RA "Adrenal hyperandrogenism is a common feature of patients with polycystic ovary syndrome (PCO). This may be due to enhanced adrenal sensitivity to ACTH. Because enhanced ovarian androgen secretion does not appear to explain this phenomenon, we explored the role of estrogen in inducing enhanced adrenal sensitivity, in that a state of relative hyperestrogenism exists in PCO." "Steroid ratio responses to oCRH suggested that 17,20-desmolase activity (delta maximum change in the ratio of A4/17-hydroxyprogesterone) was lowered with estrogen suppression and increased again after transdermal E2 administration." "In conclusion, these data provide evidence that estrogen is at least one factor that influences adrenal androgen sensitivity in PCO and may help explain the frequent finding of adrenal hyperandrogenism in this syndrome."
- "Estrogen activates the glycolytic pathway, while interfering with mitochondrial respiration. This resembles the aged or stressed metabolism, in which lactic acid is produced instead of carbon dioxide." - Ray Peat, PhD
- A 1994 publication (B. Zumoff, “Hormonal profiles in women with breast cancer,” Obstet. Gynecol. Clin. North. Am. (U.S.) 21(4), 751-772) reported that there are four hormonal features in women with breast cancer: diminished androgen production, luteal inadequacy, increased 16-hydroxylation of estradiol, and increased prolactin. The 16-hydroxylation converts estradiol into estriol. -Ray Peat, PhD
- Obstet Gynecol Clin North Am. 1994 Dec;21(4):751-72. Hormonal profiles in women with breast cancer. Zumoff B. "The literature findings on endogenous hormonal profiles in women with breast cancer are reviewed in detail. It is concluded that four sets of findings are valid: (1) diminished adrenal androgen production, probably genetic, in women with premenopausal breast cancer; (2) ovarian dysfunction (luteal inadequacy plus increased testosterone production) in breast cancer at all ages; (3) increased 16 alpha-hydroxylation of estradiol in breast cancer at all ages; and (4) evidence that prolactin is a permissive risk factor for breast cancer, and that the pregnancy-induced decrease in prolactin levels may account for the protective effect of early pregnancy against breast cancer." (via Rob Turner)
- J Natl Cancer Inst. 1986 Sep;77(3):613-6. Endogenous sex hormones, prolactin, and breast cancer in premenopausal women. Meyer F, Brown JB, Morrison AS, MacMahon B. "Forty-one women with breast cancer and 119 controls participated in a case-control study of the relation of endogenous sex hormones to breast carcinoma in premenopausal women. During the follicular phase of the menstrual cycle, one overnight urine specimen was collected. During the luteal phase, urine and blood specimens were obtained. 17 beta-Estradiol, sex hormone-binding globulin, progesterone, and prolactin were measured in plasma, whereas estrogen metabolites (estrone, estradiol, and estriol) and pregnanediol were assessed in the urine. Breast cancer was associated with high-plasma estradiol and prolactin and with low progesterone. Similar but weaker associations were observed for urinary estrogens and pregnanediol in the luteal phase." (via Rob Turner)
- "There are indications that the steroids exacerbate preexisting breast disorders, possibly by increasing prolactin levels. (Estrogens can impair B6 metabolism and therefore the synthesis of dopamine, a physiological suppressant of PRL [prolactin] secretion." - Constance R. Martin - Endocrine Physiology 1985
- "Estrogens augment PRL secretion in several ways. They lower the sensitivities of lactotrop DA receptors, and they affect DA turnover in the brain." - Constance R. Martin PhD - Endocrine Physiology 1985
- "PRL can be released in response to stress. Usually, there is a simultaneous discharge of ACTH and b-endorphin." - Constance R. Martin PhD - Endocrine Physiology
- Estrogen levels undergo substantial changes during the course of ovarian cycles. The steroids are potent stimulants for PRL release, and corresponding changes in plasma PRL have been described." - Constance R. Martin PhD - Endocrine Physiology
- "Sustained high estrogen concentrations increase both insulin requirements and insulin secretion." - Constance R. Martin PhD - Endocrine Physiology
- "Moreover, neurons involved in defeminzation contain aromatase enzymes that convert testosterone(but not DHT) to estrogen. The conclusion that estrogens are the defeminzing agents is supported by several findings." - Constance R. Martin PhD - Endocrine Physiology
- "...Similarly, in many animal species, the so-called "estrogens" do not in themselves cause estrus or heat without simultaneous progesterone treatment, hence the later hormone could be called "estrogenic" with almost equal justification. Furthermore, folliculoids [ESTROGENS} interrupt the estrous cycle in the intact rodent so that they are actually "anti-estrogenic" under ordinary circumstances of bioassay." - Hans Selye
- "It is generally assumed that habitual abortion may be due to progesterone deficiency, hypothyroidism or vitamins-e deficiency and should be treated in theses cases with progesterone, thyroid extracts and vitamin-e respectively. In theory, thyroid therapy appears to be the least well-founded, especially when applied to women without manifest signs of hypothyroidism, yet among the measures mentioned above it is most frequently claimed to have been successful." - Hans Selye
- "In the case of chronic treatment with folliculouids, the proliferation of bone tissue may cause a severe reduction of the marrow spaces, conducive to anemia. This effect is particularly marked in birds, but also clearly demonstrable in mammals." - Hans Selye
- "Injection of folliculoids into fowl eggs during the period of incubation leads to the development of intersexual males, whose reactions may vary between perfect masculine behavior." - Hans Selye
- "Folliculoids also tend to cause proliferation and increased keratinization of the dermal surface epithelium." - Hans Selye
- "Various types of stress may interfere with normal ovulation and menstruation (infectious diseases, alcoholism, dietary insufficiencies, emotional factors), and the same is true of endocrine disturbances, especially hypopituitarism, hypo- or hyperthyroidism, etc." - Hans Selye
- "Light, stress, (especially cold), dietary factors and versus stimuli are the most important non-endocrine factors which influence the production of anterior-lobe hormones [TSH, PRL, FSH, LH, GH, ACTH, etc.]." - Hans Selye
- "When the effects of perinatal gonadectomy and hormone injection were first observed, it seemed reasonable to conclude that testosterone interacts with androgen receptors in the brain to bring about defeminization. However, the concept had to be revised when it was found that estrogens mimic testosterone, whereas DHT does not. It was soon revealed that estrogen receptors begin to appear in the hypothalamus around the time of birth, and that they increase in numbers during the first few postnatal days. Moreover, neurons involved in defeminization contain aromatase enzymes that convert testosterone (but not DHT) to estrogen. The conclusion that estrogens are the defeminizing agents is supported by several findings." - Constance R. Martin
- "The chief characteristics of this principle are that it maintains fully formed corpora lute in the ovaries of intact or hypophysectomized animals and causes them to secrete luteoid hormone [PROLACTIN]. It also stimulates milk secretion, but only if the mammary glands have previously been brought to full development." - Hans Selye
- "The use of luteotrophin (prolactin) has been recommended to increase sub-normal milk secretion, but so far, results in lactating women are not particularly striking." - Hans Selye
- "Folliculoids tend to increase the prolactin content of the pituitary even when given in doses sufficient to inhibit milk secretion." - Hans Selye
- “The best established experimental observations concerning the thymus have been brought out during the last ten years by work concerned with the influence upon this organ of non-specific damage and steroid hormones. It appears that folliculoids [ESTROGEN] and to a lesser extent, even other steroid hormones, cause rapid thymus involution, not only in intact, but also in adrenalectomized animals. Non-specific damaging agents of all kinds have a similar effect only if the adrenals are intact. It has been assumed therefore, that various types of stress cause the thymus to involute through the intermediary of the adrenals.” - Hans Selye (The Textbook of Endocrinology 1947)
- “Steroid hormones cause thymic involution in proportion to their folliculoid [ESTROGEN] potency in intact, adrenalectoimized, or gonadectomized animals.” - Hans Selye (The Textbook of Endocrinology 1947)
- “Other conditions, such as exposure to nervous or even purely mental stress, forced muscular exercise, anoxia, extremes of temperature, trauma, hemorrhage or intoxication with various drugs, all produce thymus atrophy, as part of general adaption-syndrome which they elicit.” - Hans Selye
- “Following thyroidectomy, the lymphatic organs, notably the lymph nodes, thymus spleen and bone marrow, usually show moderate involution. Treatment with low doses of thyroid hormone stimulates the growth of these organs.” - Hans Selye (The Textbook of Endocrinology 1947)
- "The body temperature decreases during the shock phase of the alarm reaction, especially if defense is impeded by adrenalectomy or hypophysectomy. During the stage of resistance, on the other hand, there often is hyperthermia." - Hans Selye
- "The B.M.R is usually below normal during the shock-phase, but returns to normal during the stage of resistance." - Hans Selye
- "The blood sugar rises immediately following exposure to stress (emergency hyperglycemia); this is mainly due to the discharge of adrenaline. Later however, the blood sugar falls (often considerably below normal) and in fasting animals pronounced hypoglycemia may ensue. When the counter-shock hormones appear, the blood sugar rises again and it may reach hyperglycemic levels during the stage of resistance..." - Hans Selye
- "The liver glycogen content diminishes simultaneously with the initial hyperglycemia during the alarm reaction, presumably because the blood sugar is formed mainly at the expense of hepatic glycogen."
- "The blood volume is greatly diminished in the shock-phase, but rises to or above normal during the counter-shock-phase. It tends to remain high during the stage of resistance." - Hans Selye
- "It is possible to produce fibroids in experimental animals by injection of estrogens, and there is evidence of excess of estrogens in hypothyroid women. In hypothyroidism, there is increased activity of the pituitary gland aimed at trying to stimulate the thyroid to produce more hormone secretions, and the increased pituitary activity may spill over to affect the ovaries and increase their estrogen output." - Broda Barnes
- "Somatic growth is inhibited during exposure to stress, especially in the alarm reaction and exhaustion stages of general-adaptation-syndrome. This has been ascribed to a "shift in pituitary-hormone formation," due to the fact that in emergencies an increased production of life-maintaining corticotrophic hormones is accomplished at the expense of other, less urgently needed, hypophyseal principles such as somatorophin, the gonadotrophins, luteotrophin, etc." - Hans Selye
- "Although Selye described shock as the first (potentially lethal) phase of stress, usually followed by the corrective adaptive processes, it’s useful to think of aging in terms of a lingering partial state of shock, in which adaptation is less than perfect." - Ray Peat, PhD
- "About 50 years ago, Hans Selye (known for his discovery of the stress syndrome) gave large doses of individual steroid hormones to rats to study the range of their effects. He had previously analyzed the physiology of the stress reaction, and he observed that estrogen treatment exactly duplicated the shock phase of the stress reaction. This interferes with circulation and energy metabolism, and its physiological purpose is to cause tissue to take up water which stimulates cell division, for example in the uterus to prepare for pregnancy, and in the breasts to prepare for lactation. But none of the physiological functions of estrogen suggests that it could be beneficial in situations other than reproduction--and then only when its "shock" effect is tightly regulated by a well balanced organism--and possibly in wound healing, where its ability to stimulate cell division could be useful." - Ray Peat, PhD
- "Estrogenicity can be defined most simply as “acting the way estrogen does,” (originally, the term “estrogen” meant “producing estrus,” the female readiness to mate) and since our natural estrogen does many things, the definition is often, for practicality, based on the rapid changes produced in certain female organs by estradiol, specifically, the enlargement of the uterus by first taking up a large amount of water, and secondarily by the multiplication of cells and the production of specific proteins. A similar process occurring in the breast is also recognized as an important feature of the estrogen reaction, but as we try to define just what “estrogenicity” is, we see that there is something deeply wrong with this method of defining a hormone, because we are constantly learning more about the actions of estrogen, or of a specific form of the molecule. Calling it “the female hormone” distracted attention from its many functions in the male, and led to great confusion about its antifertility actions and its other toxicities. Many biologists called it “folliculin,” because of the ovarian follicle's significant role in its production, but the pharmaceutical industry succeeded in naming it in relation to one of its functions, and then in extending that idea of it as “the producer of female receptivity” to the even more misleading idea that it is “the female hormone.” But when people speak about the “estrogenicity” of a substance, they mean that it has properties that parallel those of “folliculin,” the particular group of ovarian hormones that includes estradiol, estrone, and estriol." - Ray Peat, PhD
- "Estriol, DES, DDT" - Ray Peat, PhD
- R. C. Merrill, "Estriol: A review," Physiol. Revs. 38(3), 463-480, 1958. "...estriol itself is a potent estrogen, contrary to the usual conception of its being just a metabolite of the more potent estrone and estradiol..."
- "Estrogen Increases Serotonin" - Rob Turner
- "Estrogen, Serotonin, and Aggression" - Rob Turner
- "Estrogen & Glucose Intolerance" - Rob Turner
- "Plasma Estrogen Does Not Reflect Tissue Concentration of Estrogen" - Rob Turner
- "Estrogen Levels Increase with Age" - Rob Turner
- "Women's monthly cycles, in which a brief estrogen dominance is followed by sustained exposure to progesterone, are probably an important factor in the renewal of the cells of the brain and other organs, as well as those of the reproductive organs. The daily rhythms of hormones and metabolism are known to be involved in the regulation of cell renewal." - Ray Peat, PhD
- "The simple availability of oxygen, and the ability to use it, are regulated by carbon dioxide and serotonin, which act in opposite directions. Carbon dioxide inhibits the release of serotonin. Carbon dioxide and serotonin are regulated most importantly by thyroid function. Hypothyroidism is characterized by increased levels of both noradrenalin and serotonin, and of other stress-related hormones, including cortisol and estrogen. Estrogen shifts the balance of the “neurotransmitters” in the same direction, toward increased serotonin and adrenalin, for example by inhibiting enzymes that degrade the monoamine 'neurotransmitters.'" - Ray Peat, PhD
- When 5 mg. of estriol was given to women intravaginally, this very large dose suppressed LH within 2 hours, and suppressed FSH in 5 hours. Given orally, 8 mg. had similar effects on LH and FSH after 30 days, and also had an estrogenic effect on the vaginal epithelium. These quick systemic effects of a "weak estrogen" are essentially those of a strong estrogen, except for the size of the dose. (Schiff, et aI., 1978)
- When administered subcutaneously, estriol induced abortions and stillbirths (Velardo, et al.)"
- "P. M. Wise has demonstrated that the "menopausal" pituitary hormones, high levels of LH and FSH, are produced because the regulatory nerves in the hypothalamus have lost their sensitivity to estrogen, not because estrogen is deficient. In fact, he showed that the nerves are desensitized precisely by their cumulative exposure to estrogen. If an animal's ovaries are removed when it is young, the regulatory nerves do not atrophy, and if ovaries are transplanted into these animals at the normally infertile age, they arc fertile. But if animals are given larger doses of estrogen during youth, those nerves atrophy prematurely, and they become prematurely infertile. The mechanism by which estrogen desensitizes and kills brain cells is now recognized as the "excitotoxic" process, in which the excitatory transmitter glutamic acid is allowed to exhaust the nerve cells. (This explains the older observations that glutamic acid, or aspartic acid, or aspartame, can cause brain damage and reproductive failure.) Cortisol also activates the excitotoxic system, in other brain cells, causing stress-induced atrophy of those cells. Progesterone and pregnenolone are recognized as inhibitors ofthis excitotoxic process." - Ray Peat, PhD