Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hamster ductus deferens cloned tumor cell line (DDT1) has been shown to contain both androgen and glucocorticoid binding activity. The androgen receptor binding site concentration is 1.07 x 10(-13) mol of testosterone/mg protein, and testosterone (T) binds with a Kd of 4.3 x 10(-10) M. Dihydrotestosterone (DHT) is also bound to the receptor with a Kd of 2.99 x 10(-10) M and the binding site concentration is 1.33 x 10(-13) mol/mg protein. The order of steroid binding affinity is DHT greater than T greater than Estradiol greater than Progesterone. Cortisol, dexamethasone, and triamcinolone acetonide do not inhibit the androgen binding in vivo or in vitro. In a cell free system antiandrogens inhibit the binding of DHT. The DDT1 cells have a separate receptor for cortisol which binds at saturation 3.44 x 10(-13) mol cortisol/mg protein and has a Kd of 4.54 x 10(-9) M. These studies provide evidence that these endocrine target cells contain specific high affinity receptors for more than one type of steroid. The glucocorticoid receptor may be important for maintaining essential undifferentiated functions while the DHT receptor gives the specific characteristics of sex hormone responsive tissues.
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PMID:The coexistence of androgen and glucocorticoid receptors in the DDT1 cloned cell line. 40 58

Intact and castrated male rats were injected daily for 10 days, beginning at 35 days of age, with either oil or one of the following steroids: testosterone propionate, dihydrotestosterone benzoate, androsterone acetate, androstenedione, androstandiol, or estradiol benzoate. Doses were 200 micrograms/rat/day for all androgens and 0.5 microgram or 2 micrograms/rat/day for estradiol. Significant increments in prolactin levels (fourfold over control values) in intact and castrated males were obtained after testosterone propionate and androstenedione treatment. Dihydrotestosterone, androsterone, and androstandiol did not induce any changes in either intact or castrated rats. Estradiol-treated males showed a four- and sevenfold increment in serum prolactin with the 0.5- and 2-microgram doses, respectively. These results suggest that androgens have a role in the control of prolactin secretion, particularly those that can be aromatized to estrogens by different tissues, including the hypothalamus.
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PMID:Effect of aromatizable androgens and estradiol on prolactin secretion in prepuberal male rats. 48 35

A galanin-like peptidergic system was demonstrated in the brain of Anguilla. A group of immunoreactive perikarya was located in the nucleus preopticus periventricularis close to the recessus preopticus. Galaninergic fibers occurred in various brain areas. Galanin identified in mammalian pituitary cells was undetectable in fish adenohypophysial cells. Estradiol increased the immunostaining of the rostral perikarya and brain fibers in both male and female European eels kept in fresh water and in female American eels in sea water. Methyltestosterone, an aromatizable androgen, increased galanin immunoreactivity in rostral perikarya and brain fibers of male European eels and female American eels. The cross-sectional area of these perikarya increased significantly after both treatments whereas cell bodies of the posteroventral hypothalamus were slightly affected. Dihydrotestosterone showed no clear effect. Fibers close to the corticotropes were sometime increased, but galanin synthesis was not induced in pituitary cells. In contrast, estradiol induced galanin synthesis in rat pituitary cells, but had a still controversed effect on hypothalamic galanin. A putative influence of galanin on the pituitary-gonadal axis is discussed as gonadal hormones diversely affect gonadotropes and gonosomatic indices in Anguilla.
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PMID:Galanin-like immunoreactivity is increased in the brain of estradiol- and methyltestosterone-treated eels. 172 86

The influence of testosterone, dihydrotestosterone (each 10 ng/ml up to 300 ng/ml) and estradiol (0.2 ng/ml up to 10 ng/ml) on the growth behaviour (cell count, [3H]thymidine uptake, cell doubling time) of subcultured human hair bulb papilla cells and hair root sheath fibroblasts was studied. Papilla cells and root sheath fibroblasts were isolated by microdissection from the same anagen hair follicles obtained from biopsies of androgen-sensitive scalp regions in 6 healthy male subjects. Dihydrotestosterone and testosterone concentrations above 30 ng/ml significantly reduced the growth of both cell types; lower doses had no effect. Estradiol had no distinct influence on the growth curves of either cell type up to 10 ng/ml, whereas higher concentrations significantly increased the growth of both cell types as shown by [3H]thymidine uptake. Papilla cells reacted more sensitively than root sheath fibroblast to dihydrotestosterone and testosterone, as shown by the growth curves, [3H]thymidine uptake, and cell doubling time.
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PMID:In vitro effects of testosterone, dihydrotestosterone and estradiol on cell growth of human hair bulb papilla cells and hair root sheath fibroblasts. 197 61

Baseline and gonadotropin-stimulated estradiol production were examined in long term cultures of human granulosa-luteal cells isolated from women undergoing in vitro fertilization. Estradiol production declined by 70% during the first 48 h in culture and was minimally stimulated by the addition of hCG to the culture medium. During subsequent culture from 48-120 h estradiol production was significantly increased over control levels by hCG concentrations greater than 0.1 IU/ml. Incubation with testosterone stimulated estradiol production 100-fold in the presence and absence of gonadotropin. hCG (0.01-10 IU/ml) stimulated a 3- to 13-fold increase in progesterone production. However, at hCG concentrations greater than 1 IU/ml, coincubation with testosterone (10(-7) M) significantly inhibited progesterone production. Dihydrotestosterone also inhibited progesterone production, but to a lesser extent than testosterone. Freshly isolated granulosa-luteal cells specifically bound small amounts of [125I]hCG (less than 1,000 cpm/10(5) cells). Glycine buffer wash was shown to reversibly remove more than 88% of bound hCG and, in freshly isolated cells, increased [125I]hCG binding by 100%. In 5-day cultures, specific [125I] hCG binding nearly doubled from 52,000 cpm/10(5) cells in control cultures to 87,000 cpm/10(5) cells in cultures treated with hCG (0-5 IU/ml). At the highest concentration of hCG (5 IU/ml), testosterone (10(-7) M) significantly inhibited the amount of [125I]hCG specifically bound. In summary, estradiol production in long term cultures of granulosa-luteal cells appears to be gonadotropin dependent. In addition, the presence of testosterone (10(-7) M) antagonizes hCG-stimulated progesterone and LH receptor production by these cells.
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PMID:Human chorionic gonadotropin stimulation of estradiol production and androgen antagonism of gonadotropin-stimulated responses in cultured human granulosa-luteal cells. 300 52

Plasma Testosterone, Dihydrotestosterone and Estradiol were determined in 72 healthy volunteers, divided into 36 beer and 36 wine drinkers, who consumed between 0.9-2.1 g ethanol/kg b.wt, simulating natural patterns of drinking. Blood samples were taken 5-10 h after drinking ceased and compared with control samples withdrawn exactly 24 h previously. For a consideration of the time variation of blood sampling, the subjects were classified as fast and slow drinkers. All groups exhibited both depressed and elevated testosterone levels, depending upon the time after drinking (fast beer drinkers) and upon the amount of alcohol (fast wine drinkers). Consumption of beer and wine significantly (P less than 0.05) inhibited dihydrotestosterone biosynthesis; depending on the time after drinking (only in beer drinkers) and blood alcohol levels (slow beer drinkers). Estradiol levels were significantly elevated (P less than 0.05-less than 0.001); correlating with the amount of beer and wine/kg b.wt, with time after drinking (fast beer drinkers), and with blood alcohol levels (fast wine drinkers). Consumption of these beverages showed different dependencies for the changed hormone levels. It is discussed whether the estrogenic constituents of beer and wine might be responsible for the enhancement of estradiol, which could contribute towards clarifying the phenomenon of feminization observed with chronic abuse of alcohol.
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PMID:Acute effects of drinking beer or wine on the steroid hormones of healthy men. 317 77

Experiments were carried out to examine the mechanism whereby 5 alpha-dihydrotestosterone (DHT) antagonizes the stimulatory effects of estrogen plus progesterone (P) on sexual receptivity (lordosis) in the ovariectomized rat. Estradiol (E2; 1 microgram s.c. in 10% ethanol) was administered in a discontinuous (pulsed) treatment regimen thought to mimic phase requirements of estrogen action; two injections of E2 were given either 6 or 12 h apart (first injection, Hour 0). Progesterone (0.5 mg in oil) was injected at Hour 20, and behavioral testing occurred at Hour 24. Dihydrotestosterone (2.5 mg s.c. in 10% ethanol/propylene glycol) inhibited lordosis when it was given before (-12 or -3 h), between (+3, or -3 and +3 h), or after (+8 h) the two E2 injections, but was not effective when given at +20 h. Significant inhibition of E2 + P-induced lordosis was achieved by 2.5 but not 1.0 or 0.2 mg DHT at -3 h, while uterine weights in the same animals were reduced significantly by 2.5 and 1.0 mg DHT. Serum E2 and DHT concentrations peaked rapidly after injection, declining to near baseline by 3 and 12 h, respectively. Induction of cytosolic progestin receptors (cPR) in the preoptic area and medial basal hypothalamus by estrogen was not prevented by DHT when animals were given the two pulsed E2 injections or daily injections of estradiol benzoate, although P was able to override the inhibitory behavioral effects of DHT in the latter but not the former group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of 5 alpha-dihydrotestosterone on sexual receptivity and neural progestin receptors in ovariectomized rats given pulsed estradiol. 405 25

Sex steroid levels in the plasma of the female Pleurodeles waltl were determined by radioimmunoassay of blood samples taken monthly from each newt during an 18-month period. Estradiol-17 beta levels were relatively high (greater than 1 ng/ml) but androgen levels were higher (2-30 ng/ml). Androgen and estradiol-17 beta levels fluctuated according to season with two annual peaks, in autumn and in March. Testosterone was the principal androgen present in this plasma. Dihydrotestosterone levels were relatively low but showed slight fluctuations during the year. 4-Androstenedione and estrone levels were very low and relatively constant throughout the seasons. Fluctuations of androgen and estradiol-17 beta levels were synchronous between the several newts studied during the year. The ratio [E2-17 beta]/[Androgen] was stable during the major part of the year (0.2-0.3) except in July and August, when it reached the value of 1.0. The seasonal variations in the steroid levels were well correlated to the morphological modifications of sexual characteristics during the year.
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PMID:Androgen and estrogen levels in the plasma of Pleurodeles waltl, Michah., during the annual cycle. II. Female cycle. 407 60

Studies within the Arab population in Israel revealed 25 pseudohermaphrodites due to 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) deficiency. Twenty-three individuals, presently living in the Gaza strip, belong to a very large inbred kinship which extends over 8 generations. All affected subjects (46, XY) were born with mild to moderate degrees of ambiguity of an apparently normal-looking female genitalia and therefore were reared as girls. In childhood, genital abnormalities consisted of a clitoral-like phallus surrounded by a chordee, non-fused labial-scrotal folds and a urogenital sinus. The testes were in the inguinal canals, or rarely, in the labial-scrotal folds. Wolffian structures were normally differentiated while Mullerian structures were absent. At puberty, subjects developed a male body habitus with abundant body hair and beard. Gynecomastia was absent. The phallus and testes enlarged to adult proportions while the prostate remained small. Together with the physical change from girls to boys they developed a male identity having erections and ejaculations, which in 7 cases led to the spontaneous adoption of a male gender role. In adults the hormonal abnormalities consisted of greatly elevated delta 4-androstenedione (delta 4) (350-1267 ng/dl) associated with subnormal testosterone (T) levels (0.9-3.1 ng/ml). Dihydrotestosterone (DHT) levels, with the exception of 1 patient, were relatively low in all cases (27-35 ng/dl). Children had low levels of delta 4, T and DHT, which were normal for age. Although from puberty on there was a significant rise of the 3 androgens, delta 4 always remained extremely elevated and T and DHT relatively low when compared to normal controls. Dexamethasone failed to suppress the androgen pattern while HCG augmented the defect, making the diagnosis possible in 2 prepubertal children. Dehydroepiandrosterone (DHEA) and 17-hydroxyprogesterone (17-OHP) levels were normal or moderately elevated. Estradiol (E2) levels were normal in children and all but 2 adults, who had high levels. LH and FSH levels were very high after puberty, but normal before. However, there was an overresponse to LHRH in all age groups. The contrast between the lack of intrauterine virilization of the external genitalia in fetuses with 17 beta-HSD deficiency versus the marked masculinization that occurs after puberty still remains a puzzling phenomenon. It is conceivable that the postpubertal development of a male phenotype with change of gender identity and role occurs due to the joint effect of delta 4, T and DHT, even though secreted in inadequate proportions. Thus masculinization in these individuals is a slow process requiring a longer period of time than that of normal puberty to be completed.
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PMID:Male pseudohermaphroditism due to 17 beta-hydroxysteroid dehydrogenase deficiency: studies on the natural history of the defect and effect of androgens on gender role. 631 Feb 48

Feminization in men occurs when the effective ratio of androgen to estrogen is lowered. Since sufficient estrogen is produced in normal men to induce breast enlargement in the absence of adequate amounts of circulating androgens, it has been generally assumed that androgens exert an antiestrogenic action to prevent feminization in normal men. We examined the mechanisms of this effect of androgens in the mouse breast. Administration of estradiol via silastic implants to castrated virgin CBA/J female mice results in a doubling in dry weight and DNA content of the breast. The effect of estradiol can be inhibited by implantation of 17 beta-hydroxy-5 alpha-androstan-3-one (dihydrotestosterone), whereas dihydrotestosterone alone had no effect on breast growth. Estradiol administration also enhances the level of progesterone receptor in mouse breast. Within 4 d of castration, the progesterone receptor virtually disappears and estradiol treatment causes a twofold increase above the level in intact animals. Dihydrotestosterone does not compete for binding to the progesterone receptor, but it does inhibit estrogen-mediated increases of progesterone receptor content of breast tissue cytosol from both control mice and mice with X-linked testicular feminization (tfm)/Y. Since tfm/Y mice lack a functional androgen receptor, we conclude that this antiestrogenic action of androgen is not mediated by the androgen receptor. Dihydrotestosterone competes with estradiol for binding to the cytosolic estrogen receptor of mouse breast, whereas 17 beta-hydroxy-5 beta-androstan-3-one (5 beta-dihydrotestosterone) neither competes for binding nor inhibits estradiol-mediated induction of the progesterone receptor. Dihydrotestosterone also promotes the translocation of estrogen receptor from cytoplasm to nucleus; the ratio of cytoplasmic-to-nuclear receptor changes from 3:1 in the castrate to 1:2 in dihydrotestosterone-treated mice. Thus, the antiestrogenic effect of androgen in mouse breast may be the result of effects of dihydrotestosterone on the estrogen receptor. If so, dihydrotestosterone performs one of its major actions independent of the androgen receptor.
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PMID:Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor. 654 71


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