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Progesterone (abbreviated as P4), also known as pregn-4-ene-3,20-dione,[5][6] is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species.[7] It belongs to a group of steroid hormones called the progestogens,[7] and is the major progestogen in the body. Progesterone is also a crucial metabolic intermediate in the production of other endogenous steroids, including the sex hormones and the corticosteroids, and plays an important role in brain function as a neurosteroid.[8]
Progesterone was independently discovered by four research groups.[9][10][11][12]
A phenyl lithium to produce the phosphonium ylide 8. The ylide 8 is reacted with an aldehyde to produce the alkene 9. The ketal protecting groups of 9 are hydrolyzed to produce the diketone 10, which in turn is cyclized to form the cyclopentenone 11. The ketone of 11 is reacted with methyl lithium to yield the tertiary alcohol 12, which in turn is treated with acid to produce the tertiary cation 13. The key step of the synthesis is the π-cation cyclization of 13 in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce 14. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as biomimetic. In the next step the enol orthoester is hydrolyzed to produce the ketone 15. The cyclopentene A-ring is then opened by oxidizing with ozone to produce 16. Finally, the diketone 17 undergoes an intramolecular aldol condensation by treating with aqueous potassium hydroxide to produce progesterone.[144]
Progesterone can also be made from the stigmasterol found in soybean oil also. c.f. Percy Julian.
An economical semisynthesis of progesterone from the plant steroid diosgenin isolated from yams was developed by Russell Marker in 1940 for the Parke-Davis pharmaceutical company.[106] This synthesis is known as the Marker degradation. Additional semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, cortisone can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in chloroform to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.[138]
Vaginally dosed progesterone is being investigated as potentially beneficial in preventing preterm birth in women at risk for preterm birth. The initial study by Fonseca suggested that vaginal progesterone could prevent preterm birth in women with a history of preterm birth.[127] According to a recent study, women with a short cervix that received hormonal treatment with a progesterone gel had their risk of prematurely giving birth reduced. The hormone treatment was administered vaginally every day during the second half of a pregnancy.[128] A subsequent and larger study showed that vaginal progesterone was no better than placebo in preventing recurrent preterm birth in women with a history of a previous preterm birth,[129] but a planned secondary analysis of the data in this trial showed that women with a short cervix at baseline in the trial had benefit in two ways: a reduction in births less than 32 weeks and a reduction in both the frequency and the time their babies were in intensive care.[130] In another trial, vaginal progesterone was shown to be better than placebo in reducing preterm birth prior to 34 weeks in women with an extremely short cervix at baseline.[131] An editorial by Roberto Romero discusses the role of sonographic cervical length in identifying patients who may benefit from progesterone treatment.[132] A meta-analysis published in 2011 found that vaginal progesterone cut the risk of premature births by 42 percent in women with short cervixes.[133] The meta-analysis, which pooled published results of five large clinical trials, also found that the treatment cut the rate of breathing problems and reduced the need for placing a baby on a ventilator.[134]
For comparative purposes, mid-luteal serum levels of progesterone are above 5–9 ng/ml,[124] plasma levels in the first 4 to 8 weeks of pregnancy are 25–75 ng/ml,[25] and serum levels at term are typically around 200 ng/ml.[25]
Progesterone can also be administered alternatively via subcutaneous injection, with the aqueous new formulation Prolutex being intended specifically for once-daily administration by this route.[125][126] This formulation is rapidly absorbed and has been found to result in higher serum peak progesterone levels relative to intramuscular oil formulations.[126] In addition, subcutaneous injection of progesterone is considered to be easier, safer (less risk of injection site reactions), and less painful relative to intramuscular injection.[126]
Due to the high concentrations achieved, progesterone by intramuscular injection at the usual clinical dose range is able to suppress gonadotropin secretion from the pituitary gland, demonstrating antigonadotropic efficacy.[24]
With intramuscular injection of 10 mg progesterone suspended in vegetable oil, maximum plasma concentrations (Cmax) are reached at approximately 8 hours after administration, and serum levels remain above baseline for about 24 hours.[24] Doses of 10 mg, 25 mg, and 50 mg via intramuscular injection result in mean maximum serum concentrations of 7 ng/mL, 28 ng/mL, and 50 ng/mL, respectively.[24] With intramuscular injection, a dose of 25 mg results in normal luteal phase serum levels of progesterone within 8 hours, and a 100 mg dose produces mid-pregnancy levels.[124] At these doses, serum levels of progesterone remain elevated above baseline for at least 48 hours.[124]
With vaginal and rectal administration, a 100 mg dose of progesterone results in peak levels at 4 hours and 8 hours after dosing, respectively, with the levels achieved being in the serum luteal phase range.[124] Following peak serum concentrations, there is a gradual decline in plasma levels, and after 24 hours, serum levels typical of the follicular phase are reached.[124]
Equivalent doses of transdermal progesterone are about 5–7 times lower relative to oral administration.[1] This is due to the fact transdermal administration bypasses first-pass metabolism.[1] As such, 20–30 mg/day transdermal progesterone is equivalent to about 100–200 mg/day oral progesterone.[1]
Progesterone, when taken orally, undergoes gastrointestinal (especially hepatic) metabolism to form hydroxylated metabolites, which in turn are metabolized into sulfate and glucuronide derivatives.[123] Enzymes involved in the hepatic metabolism of progesterone include, particularly, CYP2C19 and CYP3A4, as well as CYP2C9.[2][3]
Progesterone is a weak but significant agonist of the PXR, and has been found to induce several hepatic cytochrome P450 enzymes, such as CYP3A4, especially when concentrations are high, such as with pregnancy range levels.[43][44][45][46] As such, progesterone may have the potential to accelerate the clearance of various drugs, especially with oral administration (which results in supraphysiological levels of progesterone in the liver), as well as with the high concentrations achieved with sufficient injection dosages.
There are several notable drug interactions with progesterone. Selective serotonin reuptake inhibitors (SSRIs) may increase the GABAA receptor-related central depressant effects of progesterone by enhancing its conversion into 5α-dihydroprogesterone and allopregnanolone via activation of 3α-HSD.[117] Progesterone potentiates the sedative effects of benzodiazepines and ethanol.[118] Notably, there is a case report of progesterone abuse alone with very high doses.[119] 5α-Reductase inhibitors such as finasteride and dutasteride, as well as inhibitors of 3α-HSD such as medroxyprogesterone acetate, inhibit the conversion of progesterone into its inhibitory neurosteroid metabolites, and for this reason, may have the potential to block or reduce its sedative effects.[120][121][122]
OMP is prescribed in divided doses of 25–400 mg/daily,[111] but in the range of 100–300 mg per day most commonly. Oral doses of 100–200 mg will result in serum progesterone levels greater than 10 ng/mL.[112] Notably, a portion of progesterone is converted into 5α-dihydroprogesterone and allopregnanolone (a conversion that is catalyzed by the enzymes 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD) and occurs in the liver, reproductive endocrine tissues, skin, and the brain),[27] which are neurosteroids and potent potentiators of GABAA receptors.[112][113] It is for this reason that common reported side effects of progesterone include dizziness, drowsiness or sedation, sleepiness, and fatigue, especially at high doses.[112][113] As a result, some physicians may instruct their patients to take their progesterone before bed.[112] Both oral and intramuscularly injected progesterone produce sedative effects, indicating that first-pass metabolism in the liver is not essential for the conversion to take place.[114][115][116] Moreover, the sedative effects occur in both men and women, indicating a lack of sex-specificity of the effects.[114]
Progesterone has a relatively short half-life in the body. As such, OMP is usually prescribed for twice or thrice-daily administration or once-daily administration when taken by injection.[4] Via the oral route, peak concentrations are seen about 2–3 hours after ingestion, and the half-life is about 16–18 hours.[4] Significantly elevated serum levels of progesterone are maintained for about 12 hours, and levels do not return to baseline until at least 24 hours have passed.[4]
The route of administration impacts the effects of progesterone. OMP has a wide inter-individual variability in absorption and bioavailability. In contrast, progestins are rapidly absorbed with a longer half-life than progesterone and maintain stable levels in the blood.[109] The absorption and bioavailability of OMP is increased approximately two-fold when it is taken with food.[110]
Transdermal products made with progesterone USP (i.e., "natural progesterone") do not require a prescription. Some of these products also contain "wild yam extract" derived from Dioscorea villosa, but there is no evidence that the human body can convert its active ingredient (diosgenin, the plant steroid that is chemically converted to produce progesterone industrially[106]) into progesterone.[107][108]
Progesterone, when taken orally, has very poor pharmacokinetics, including low bioavailability (only about 10–15% reaches the bloodstream)[1] and a half-life of only about 5 minutes, unless it is micronized.[4][7] As such, it is sold in the form of oil-filled capsules containing micronized progesterone for oral use (Utrogestan, Prometrium, Microgest), termed oral micronized progesterone (OMP).[4][104] Progesterone is also available in the forms of vaginal or rectal suppositories or pessaries (Cyclogest),[104] transdermally-administered gels or creams (Crinone, Endometrin, Progestogel, Prochieve),[104][105] or via intramuscular or subcutaneous injection of a vegetable oil solution (Progesterone, Strone).[4][24][104]
The use of progesterone and its analogues have many medical applications, both to address acute situations and to address the long-term decline of natural progesterone levels. Because of the poor bioavailability of progesterone when taken orally, many synthetic progestins have been designed with improved oral bioavailability and have been used long before progesterone formulations became available.[99] Progesterone was approved by the United States Food and Drug Administration as vaginal gel on July 31, 1997,[100] an oral capsule on May 14, 1998[101] in an injection form on April 25, 2001[102] and as a vaginal insert on June 21, 2007.[103] Progesterone is marketed under a large number of different brand names throughout the world.[104]
Progesterone enhances the function of serotonin receptors in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance serotonin activity such as nicotine, alcohol, and cannabis when their progesterone levels fall below optimal levels.[89]
The clinical trials for progesterone as a treatment for traumatic brain injury have only recently begun. ProTECT, a phase II trial conducted in Atlanta at Grady Memorial Hospital in 2007, the first to show that progesterone reduces edema in humans. Since then, trials have moved on to phase III. The National Institute of Health began conducting a nationwide phase III trial in 2011 led by Emory University.[75] A global phase III initiative called SyNAPSe®, initiated in June 2010, is run by a U.S.-based private pharmaceutical company, BHR Pharma, and is being conducted in the United States, Argentina, Europe, Israel and Asia.[87][88] Approximately 1,200 patients with severe (Glasgow Coma Scale scores of 3-8), closed-head TBI will be enrolled in the study at nearly 150 medical centers.
One study looks at a combination of progesterone with estrogen. Both progesterone and estrogen are known to have antioxidant-like qualities and are shown to reduce edema without injuring the blood-brain barrier. In this study, when the two hormones are administered alone it does reduce edema, but the combination of the two increases the water content, thereby increasing edema.[86]
Vitamin D and progesterone separately have neuroprotective effects after traumatic brain injury, but when combined their effects are synergistic.[85] When used at their optimal respective concentrations, the two combined have been shown to reduce cell death more than when alone.
Not only does progesterone help prevent further damage, it has also been shown to aid in neuroregeneration. One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in edema levels by increasing the concentration of macrophages and microglia sent to the injured tissue.[81][83] This was observed in the form of reduced leakage from the blood brain barrier in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have antioxidant properties, reducing the concentration of oxygen free radicals faster than without.[82] There is also evidence that the addition of progesterone can also help remyelinate damaged axons due to trauma, restoring some lost neural signal conduction.[82] Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain.[84] This helps new vasculature to grow around scar tissue which helps repair the area of insult.
Progesterone has also been shown to prevent apoptosis in neurons, a common consequence of brain injury.[74] It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated caspase 3 and cytochrome c.
Damage incurred by traumatic brain injury is believed to be caused in part by mass depolarization leading to excitotoxicity. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the voltage-dependent calcium channels that trigger neurotransmitter release.[81] It does so by manipulating the signaling pathways of transcription factors involved in this release. Another method for reducing the excitotoxicity is by up-regulating the GABAA, a widespread inhibitory neurotransmitter receptor.[82]
The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma.[80]
Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to traumatic brain injury and this protective effect has been hypothesized to be caused by increased circulating levels of estrogen and progesterone in females.[76] A number of additional animal studies have confirmed that progesterone has neuroprotective effects when administered shortly after traumatic brain injury.[77] Encouraging results have also been reported in human clinical trials.[78][79]
Studies as far back as 1987 show that female sex hormones have an effect on the recovery of traumatic brain injury.[74] In these studies, it was first observed that pseudopregnant female rats had reduced edema after traumatic brain injury. Recent clinical trials have shown that among patients that have suffered moderate traumatic brain injury, those that have been treated with progesterone are more likely to have a better outcome than those who have not.[75]
The tendency for progesterone to have a regulatory effect, the presence of progesterone receptors in many types of body tissue, and the pattern of deterioration (or tumor formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.
Since most progesterone in males is created during testicular production of testosterone, and most in females by the ovaries, the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of progestogens in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.
Neurosteroids are neuromodulators, and are neuroprotective, neurogenic, and regulate neurotransmission and myelination.[73] The effects of progesterone as a neurosteroid are mediated predominantly through its interactions with non-nuclear PRs, namely the mPRs and PGRMC1, as well as certain other receptors, such as the σ1 and nACh receptors.
Progesterone, like pregnenolone and dehydroepiandrosterone (DHEA), belongs to an important group of endogenous steroids called neurosteroids. It can be synthesized within the central nervous system and also serves as a precursor to another major neurosteroid, allopregnanolone.
Dr. Diana Fleischman, of the University of Portsmouth, and colleagues examined the relationship between progesterone and sexual attitudes. Their research was published in the Archives of Sexual Behavior.[70] They found that women who have higher levels of progesterone are more likely to be open to the idea of engaging in sexual behaviour with other women.[71] Similarly, when heterosexual men are subtly reminded of the importance of having male friends and allies, they report more positive attitudes toward engaging in sexual behaviour with other men. This pattern is particularly dramatic in men who have high levels of progesterone.[72]
Progesterone and its neurosteroid active metabolite allopregnanolone appear to be importantly involved in sex drive in females.[69]
Progesterone also appears to be involved in the hormone replacement therapy, the combination of natural progesterone or the pure, non-androgenic progestin dydrogesterone with estrogen has been found not to do so.[67][68] In fact, progesterone or dydrogesterone added to estrogen appear to decrease the risk of breast cancer relative to estrogen alone.[67]
Though to a far lesser extent than estrogen, which is the major mediator of breast ductal development (via ERα, specifically),[63][64] progesterone has been found to be involved in ductal development as well.[65] PR knockout mice or mice treated with the PR antagonist mifepristone show delayed but otherwise normal ductal development at puberty.[65] In addition, mice modified to have overexpression of PRA display ductal hyperplasia,[62] and progesterone induces ductal growth in mouse mammary gland.[65] Progesterone mediates ductal development mainly via the induction of amphiregulin, the same growth factor that estrogen primarily induces to mediate ductal development.[65] These findings suggest that, while not essential for full ductal development, progesterone seems to play a potentiating or accelerating role in estrogen-mediated ductal development, at least in mice.[65]
Progesterone plays an important role in mammary gland development in females. In conjunction with prolactin, it mediates lobuloalveolar maturation of the breasts during pregnancy to allow for milk production, and thus lactation and breastfeeding after childbirth.[61] Estrogen is required for progesterone to mediate lobuloalveolar maturation, as it induces expression of the PR in breast tissue.[50][51][52] Moreover, it has been found that RANKL is a critical downstream mediator of progesterone-mediated lobuloalveolar development.[62] Knockout mice of RANKL show an almost identical mammary phenotype relative to PR knockout mice, including normal mammary ductal development but complete failure of the development of lobuloalveolar structures.[62]
The fetus metabolizes placental progesterone in the production of adrenal steroids.
Progesterone is sometimes called the "hormone of pregnancy",[59] and it has many roles relating to the development of the fetus:
Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified.[54] Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes,[55] slow calcium oscillations,[56] now thought to possibly regulate motility.[57] Interestingly, progesterone has also been shown to demonstrate effects on octopus spermatozoa.[58]
Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.[53]
Progesterone has a number of physiological effects that are amplified in the presence of estrogens. Estrogens through estrogen receptors (ERs) induce or upregulate the expression of the PR.[49] One example of this is in breast tissue, where estrogens allow progesterone to mediate lobuloalveolar development.[50][51][52]
Progesterone binds extensively to plasma proteins, including albumin (50–54%) and transcortin (43–48%).[24] It has similar affinity for albumin relative to the PR.[25]
Progesterone modulates the activity of CatSper (cation channels of sperm) voltage-gated Ca2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (chemotaxis). As a result, it has been suggested that substances that block the progesterone binding site on CatSper channels could potentially be used in male contraception.[47][48]
Progesterone and some of its metabolites, such as 5β-dihydroprogesterone, are agonists of the pregnane X receptor (PXR),[41] albeit weakly so (EC50 >10 µM).[42] In accordance, progesterone induces several hepatic cytochrome P450 enzymes,[43] such as CYP3A4,[44][45] especially during pregnancy when concentrations are much higher than usual.[46] Premenopausal women have been found to have greater CYP3A4 activity relative to men and postmenopausal women, and it has been inferred that this may be due to the higher progesterone levels present in premenopausal women.[44]
Progesterone, through its neurosteroid active metabolites such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a positive allosteric modulator of the GABAA receptor.[40]
Progesterone is the most important progestogen in the body, the result of its action as a potent agonist of the nuclear progesterone receptor (nPR) (with an affinity of KD = 1 nM[25]).[7] In addition, progesterone is an agonist of the more recently discovered membrane progesterone receptors (mPRs),[32] as well as a ligand of the PGRMC1 (progesterone receptor membrane component 1; formerly known as the σ2 receptor).[33] Moreover, progesterone is also known to be an antagonist of the σ1 receptor,[34][35] a negative allosteric modulator of the nACh receptors,[8] and a potent antagonist of the mineralocorticoid receptor (MR).[36] Progesterone prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and glucocorticoids such as cortisol and corticosterone,[36] and produces antimineralocorticoid effects, such as natriuresis, at physiological concentrations.[37] In addition, progesterone binds to and behaves as a partial agonist of the glucocorticoid receptor (GR), albeit with very low potency (EC50 >100-fold less relative to cortisol).[38][39]
Blood test results should always be interpreted using the reference ranges provided by the laboratory that performed the results. Example reference ranges are listed below.
Progesterone levels are relatively low in children and postmenopausal women.[29] Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.
In women, progesterone levels are relatively low during the preovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase, as shown in diagram below. Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If pregnancy occurs, human chorionic gonadotropin is released maintaining the corpus luteum allowing it to maintain levels of progesterone. Between 7–9 weeks the placenta begins to produce progesterone in place of the corpus luteum, this process is named the luteal-placental shift.[28] After the luteal-placental shift progesterone levels start to rise further and may reach 100-200 ng/ml at term. Whether a decrease in progesterone levels is critical for the initiation of labor has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.
Progesterone is reduced to its much less potent progestogen metabolite 20α-hydroxyprogesterone by the 20α-hydroxysteroid dehydrogenases AKR1C1 and AKR1C3.[26] In addition, progesterone is converted into its active progestogen and neurosteroid metabolite 5α-dihydroprogesterone by 5α-reductase, which in turn can be converted into the non-progestogen but even more potent neurosteroid allopregnanolone by 3α-hydroxysteroid dehydrogenase.[27] Progesterone is converted into 17α-hydroxyprogesterone and deoxycorticosterone by 17α-hydroxylase and 21-hydroxylase, respectively. 17α-Hydroxyprogesterone serves as a precursor for the androgens and estrogens, and deoxycorticosterone is a corticosteroid and a precursor for other corticosteroids as well.
Progesterone is metabolized mainly in the liver.[24] It is reduced to a variety of active and inactive metabolites, including pregnanediol, pregnanetriol, and pregnanolone (pregnanedione).[24] These metabolites are subsequently conjugated into glucuronide and sulfate forms.[24] In urine, pregnanediol glucuronide is the major metabolite of progesterone.[25] It has been found to constitute about 30% of an injection of progesterone.[25]
Pregnenolone and progesterone can also be synthesized by yeast.[23]
Progesterone in turn (see lower half of figure to the right) is the precursor of the mineralocorticoid aldosterone, and after conversion to 17α-hydroxyprogesterone (another natural progestogen) of cortisol and androstenedione. Androstenedione can be converted to testosterone, estrone and estradiol.
The conversion of pregnenolone to progesterone takes place in two steps. First, the 3-hydroxyl group is oxidized to a keto group (4) and second, the double bond is moved to C-4, from C-5 through a keto/enol tautomerization reaction.[22] This reaction is catalyzed by 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase.
Cholesterol (1) undergoes double oxidation to produce 20,22-dihydroxycholesterol (2). This vicinal diol is then further oxidized with loss of the side chain starting at position C-22 to produce pregnenolone (3). This reaction is catalyzed by cytochrome P450scc.
In mammals, progesterone (6), like all other steroid hormones, is synthesized from pregnenolone (3), which in turn is derived from cholesterol (1) (see the upper half of the figure to the right).
Many other Dioscorea species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are Dioscorea villosa and Dioscorea polygonoides. One study showed that the Dioscorea villosa contains 3.5% diosgenin.[19] Dioscorea polygonoides has been found to contain 2.64% diosgenin as shown by gas chromatography-mass spectrometry.[20] Many of the Dioscorea species that originate from the yam family grow in countries that have tropical and subtropical climates.[21]
Another plant that contains substances readily convertible to progesterone is Dioscorea pseudojaponica native to Taiwan. Research has shown that the Taiwanese yam contains saponins — steroids that can be converted to diosgenin and thence to progesterone.[18]
In at least one plant, Juglans regia, progesterone has been detected.[15] In addition, progesterone-like steroids are found in Dioscorea mexicana. Dioscorea mexicana is a plant that is part of the yam family native to Mexico.[16] It contains a steroid called diosgenin that is taken from the plant and is converted into progesterone.[17] Diosgenin and progesterone are found in other Dioscorea species as well.
An additional animal source of progesterone is milk products. After consumption of milk products the level of bioavailable progesterone goes up.[14]
During human pregnancy, progesterone is produced in increasingly high amounts by the ovaries and placenta. At first, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropin (hCG) from the conceptus. However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal corticosteroids. At term the placenta produces about 250 mg progesterone per day.
Progesterone is produced in high amounts in the ovaries (by the corpus luteum) from the onset of puberty to menopause, and is also produced in smaller amounts by the adrenal glands after the onset of adrenarche in both males and females. To a lesser extent, progesterone is produced in nervous tissue, especially in the brain, and in adipose (fat) tissue, as well.
Like other steroids, progesterone consists of four interconnected cyclic hydrocarbons. Progesterone contains ketone and oxygenated functional groups, as well as two methyl branches. Like all steroid hormones, it is hydrophobic.
[13]
Abortion, Childbirth, Assisted reproductive technology, Obstetrics, Menstrual cycle
Ghrelin
Progesterone, Dehydroepiandrosterone, Birds, Glucocorticoid, Pregnenolone
Danazol, Ketoconazole, Pregnenolone, Progesterone, 17-Hydroxyprogesterone
Danazol, 17-Hydroxyprogesterone, Ketoconazole, Progesterone, Aminoglutethimide
Danazol, Spironolactone, Ketoconazole, Aminoglutethimide, Cyanoketone
Testosterone, Progesterone, Cholesterol, Pregnenolone, Dehydroepiandrosterone