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PubMed2003

Urinary testosterone-metabolite levels and dominance rank in male and female bonobos (Pan paniscus).

The correlation between testosterone (T) and dominance rank may vary among species, and is expected to become stronger as the importance of aggressive competition for rank increases. However, it may also vary among social situations within a species, showing a stronger correlation during socially unstable periods. Knowledge on this topic in great apes, especially in females, is scant. This study presents the first data on the relationship between T and dominance rank in both sexes of the bonobo ( Pan paniscus). For each period (four socially unstable and two stable ones), linear rank orders were determined and subsequently correlated with the accompanying mean urinary T-metabolite concentrations (measured as immunoreactive 5alpha-androstan-17alpha-ol-3-one). No correlation between these two variables was found for either sex among individuals during socially unstable or stable periods. Also, within an individual over the six periods, no relationship of T with rank could be demonstrated. These results suggest that either the outcomes of aggressions have no influence on T levels, or such clear outcomes appear insufficiently frequent to affect T levels over longer periods. Even during the unstable periods, the rate of aggressions was not higher than during stable periods, suggesting that frequencies of aggression have little effect on rank. Further analyses indeed demonstrated no correlation between frequencies of overall aggressions or any type of aggressive behavior separately, or rank. Perhaps factors other than the frequency of displayed aggressions alone have a marked influence on a bonobo's rank, for example, coalition partners. Overall, in bonobos, T apparently does not form a physiological reflection of social status.

Aggression↗
PubMed2000

Hormonal aspects of sexual dysfunction: the therapeutic use of exogenous androgens in men and women.

Hormones exert a pervasive influence on sexual activity. Androgens are involved in the initiation and maintenance of libido and spontaneous arousal. In recent years, the clinical use of exogenous androgens for treatment of sexual dysfunction has received a great deal of attention. Good evidence exists that such treatment is effective for arousal difficulties in men and women in the setting of a hypo-androgenic state. This article reviews the relationship between androgens and sexual function.

Clinical Trials as Topic↗
PubMed1981

Evidence for an androgen receptor in the human placenta.

A steroid-binding protein was examined in human placental and nuclei which had several characteristics of an androgen receptor. It binds R 1881 (methyltrienolone), a steroid specific for androgen receptors, with high affinity (dissociation constant equals 1.3 to 50 nM) and low capacity (n equals 1.2 to 21 moles/mg of protein). The steroid-binding protein is found in the nuclei as well as the cytosol of the placenta but is not found in either the cytosol or the nuclei of fetal membranes; thus, it is tissue-specific. Among the natural steroids, 5 alpha-dihydrotestosterone competes most efficiently with R1881 for binding to the protein. Testosterone is the next best competitor. When the ranges of dissociation constants and concentrations of binding sites for placentas of various gestational periods are compared, not significant differences are observed between period of gestation and magnitude of binding constants.

Binding, Competitive↗
PubMed1989

Androgen receptor in rat liver: characterization and separation from a male-specific estrogen-binding protein.

Many liver processes are sexually dimorphic. In particular, the microsomal content of specific enzymes and the synthesis of specific proteins are under sex steroid hormone control. Because the liver of male rats is strikingly androgen responsive, we sought evidence for an androgen receptor in this tissue. We detected and characterized both cytosolic and nuclear androgen-binding proteins. Both forms bind [3H]R1881 (methyltrienolone, 17 beta-hydroxy-17 alpha-methyl-4,9,11-estratriene-3-one) with the high affinity, low capacity, and specificity for androgens and antiandrogens characteristic of androgen receptors. No high-affinity binding of [3H]DHT could be detected in unfractionated cytosol because of the rapid metabolism of this ligand; however, binding of a DHT metabolite to the high-capacity male-specific estrogen binder (MEB) of cytosol was observed. Both gel filtration and heparin-Sepharose affinity chromatography separate the cytosolic androgen receptor from MEB. Incubation of cytosol in the absence of sodium molybdate resulted in androgen-binding activity which was retained by DNA-cellulose. Castration of male rats results in a time-dependent loss of both cytosolic and nuclear androgen binding, as well as a loss in MEB activity. Androgen-binding activity is low in livers from female rats, but can be induced by testosterone treatment. An intact pituitary is necessary for maintenance of androgen-binding activity, as hypophysectomy results in complete loss of activity.

Animals↗
PubMed1985

Effects of testosterone and its metabolites in relation to androgen-binding activity in murine submandibular salivary glands.

The relative potencies of testosterone (T), testosterone propionate (TP) and other related steroids (5 alpha-dihydrotestosterone, DHT; 5 alpha-androstane-3 alpha, 17 beta-diol, alpha-diol; 5 alpha-androstane-3 beta, 17 beta-diol, beta-diol) in restoring some morphological and functional characteristics of submandibular gland (SMG) were investigated in castrated mice. The steroids restored to near-control values the glandular weight and total protein content, alpha-diol and TP being the most effective compounds tested; with regard to proteolytic activity stimulation, beta-diol was more effective than DHT. The alpha-diol metabolite was unique in significantly increasing DNA synthesis. In competition studies, alpha-diol and beta-diol were ineffective in displacing the specifically bound [3H]-R1881 from the SMG androgen-binding macromolecules. Thus T can elicit its effects on SMG without the need of prior conversion to DHT; there must be alternative, receptor-independent mechanisms whereby alpha- and beta-diol exert trophic/metabolic effects on murine SMG.

Androstane-3,17-diol↗
PubMed1991

Effects of androgen on intracellular calcium of LNCaP cells.

Mibolerone (dimethylnortestosterone) or 5 alpha-dihydrostestosterone (DHT) increase intracellular calcium (Ca2+i) of human prostate cancer cells (LNCaP) as early as 2 min after treatment. These effects were concentration-dependent (10(-6)-10(-12) M) and they were blocked by preincubation with hydroxyflutamide (10(-6) M). Verapamil (10(-6) M) also suppressed the mibolerone (10(-6) M)-induced increase in Ca2+i, in cells which were previously exposed to 1 mM CaCl2 introduced in a Ca(2+)-free media. The results indicate that androgens elicit changes in Ca2+i in LNCaP cells as a result of Ca2+ influx through L-type channels in the plasma membrane. Since androgens are involved in the regulation of prostate cell division and growth, these findings suggest that calcium is involved in metabolic and mitogenic responses to steroid hormone in target cells.

Calcium↗
PubMed1988

Sex differences in nuclear androgen receptors in guinea pig brain and the effects of an alpha 2 noradrenergic blocker on androgen receptors.

The binding of the synthetic androgen, [3H]methyltrienolone (R1881) to nuclear androgen receptors (NAR) was studied in various brain areas of gonadectomized male and female guinea pigs treated for 3 days with 2 mg testosterone propionate. The Scatchard analysis of salt-extracted NAR showed a single, high-affinity receptor with a Kd of 0.152 nM and maximum binding sites (Bmax) of 161.9 fmol/mg DNA. The concentration of NAR was highest in the hypothalamus (HYPO) and preoptic area (POA) in both males and females. Lower receptor levels were detected in the amygdala and cortex. NAR levels were significantly lower in the POA of females than in males. Systemic injection of prazosin, an alpha 1-adrenergic antagonist had no effect on NAR concentrations, but an alpha 2-antagonist, idazoxan, significantly reduced the binding of [3H]R1881 to NAR in both HYPO and POA. The reduction in binding of the ligand to receptor was not due to alterations in affinity of NAR, but rather to the decline in the number of receptors.

Adrenergic alpha-Antagonists↗
PubMed1988

Distribution of androgen receptor in microdissected brain areas of the female baboon (Papio cynocephalus).

We measured androgen receptors in the brain and pituitary of 4 female baboons (Papio cynocephalus) by the in vitro binding of methyltrienolone (R1881) to cytosols from 17 brain subregions as well as anterior and posterior pituitaries. High levels of AR were detected in anterior (22.1 +/- 7.1 (S.E.M.) fmol/mg protein) and posterior pituitary (12.6 +/- 3.3 fmol/mg protein). In brain tissue, the highest androgen receptor levels were found in the infundibular nucleus/median eminence (9.4 +/- 2.3 fmol/mg protein), ventromedial nucleus (6.3 +/- 1.7 fmol/mg protein) and periventricular area (4.9 +/- 1.3 fmol/mg protein). Saturation analysis of anterior pituitary and brain tissue (pool of hypothalamic, preoptic area, amygdala and septum remaining after microdissection of brain nuclei) showed that [3H]R1881 binds to the androgen receptor with high specificity and affinity (Kd = 1.25 x 10(-10) M, 0.45 x 10(-10) M, in anterior pituitary and HPA cytosol, respectively). Serum testosterone levels were low in all animals (0.59 +/- 0.26 ng/ml). With these data we described the quantitative distribution of androgen receptor in the pituitary and in specific brain nuclei in a species of nonhuman primate. The distribution is similar in many respects to that described in the male rat and the data suggest a conservation of androgen receptor distribution across species.

Animals↗
PubMed1996

Spatial working memory is preserved in rats treated with anabolic-androgenic steroids.

The effects of anabolic-androgenic steroid (AAS) compounds on spatial working memory were evaluated in male rats. Thirty days of administration of a high dose of three individual AAS compounds (17 alpha-methyltestosterone, methandrostenolone, or testosterone cypionate) had no effects on spatial memory or motivation as tested on a delayed non-match-to-sample radial arm maze task. Administration of these AAS compounds at doses within the human abuse range does not impair spatial working memory in rats.

Anabolic Agents↗
PubMed1979

RMI 12,936 and pseudopregnancy in rats.

RMI 12,936, when injected subcutaneously at a dose of 2 mg, either on Day 6 of psuedopregnancy (PSP-6) or on PSP-6,7 and 8, shortened the duration of PSP from 12.3 +/- 0.3 (control) to 8.3 +/- 0.1 or 8.7 +/- 0.2 days, respectively. During PSP, plasma progesterone (delta 4P) levels in the peripheral plasma showed a trend of decrease by PSP-9 (52.0 +/- 4.6 on PSP-8 to 42.3 +/- 3.1 ng/ml on PSP-9). Administration of RMI 12,936 on PSP-6 resulted in a significant decrease in delta 4P and pregnenolone (delta 5P) within 24 hr after treatment but caused no apparent changes in 20 alpha-dihydroprogesterone (20 alpha-DHP) levels. However, a significant decrease of delta 4P/20 alpha DHP ratio was encountered 24 hr after RMI 12,936 treatment. The persistent occurrence of proestrous smear after PSP termination, but absence of estrous vaginal cytology, might be attributed to the slight estrogenicity of RMI 12,936. After the premature termination of pseudopregnancy induced by RMI 12,936, the female rats were sexually receptive for at least 3 weeks but failed to conceive, suggesting that this compound has a prolonged contraceptive effect.

Androstenols↗
PubMed1979

Termination of pregnancy in the rat by RMI 12,936.

Administration of a steroid RMI 12,936 (2 MG) ON DAY 8 OF PREGNANCY RESULted in an interruption of gestation within 5 days. No significant changes in progesterone (delta 4P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and pregnenolone (delta 5P) were recorded during the course of termination of pregnancy by RMI 12,936. However, a significant rise in serum delta 4P and hypertropic corpora lutea were evident on day 13 of pregnancy when all treated females showed dead conceptus. The placental tissue was still present at the time of pregnancy termination. On the other hand, serum LH levels was significantly suppressed 24 hr after the treatment and maintained at a very low level. The reduction of LH might be due to a lowered hypophyseal sensitivity towards LH-RH. The occurrence of in utero dead fetus without interference of delta 4P production suggests that in the rat RMI 12,936-induced termination of pregnancy is due to its embryotoxic rather than luteolytic effect. Although the treated females did not return to normal estrous cycles for a period of 2 weeks after pregnancy termination, they were sexually receptive. Successful mating resulted in normal pregnancy which occurred 30-35 days after RMI 12,936 treatment.

Abortifacient Agents↗
PubMed1989

Action of sex steroid hormones on temperature-induced sex determination in the snapping turtle (Chelydra serpentina).

Administration of exogenous estradiol benzoate (EB) or an estrogen agonist, R2858, into eggs of snapping turtles caused all embryos incubated at male-producing temperatures to develop as females, whereas testosterone propionate (TP) caused 42% of the embryos to develop as females. Some of the embryos treated with EB, R2858, or TP also had hypertrophied oviducts. Neither dihydrotestosterone (DHT) nor cholesterol had any apparent effect on the sex determination of embryos incubated at male-producing temperatures. Injections of TP, DHT, the androgen agonist R1881, or cholesterol had no apparent effect on sex determination of embryos incubated at female-producing temperatures. Administration of estradiol antiserum or testosterone antiserum resulted in some individuals having undifferentiated or ambiguous gonads. Although both exogenous estrogens and androgens can induce embryonic gonads to develop as ovaries, the findings of this study indicate that estrogen is the female-inducing hormone and that androgens may feminize gonads via aromatization to estrogen. Furthermore, the results of the antisera injection suggest that endogenous steroid hormones may have a natural role in gonadal differentiation of reptiles with environmental sex determination.

Animals↗