Testosterone

About: Testosterone is a research topic. Over the lifetime, 23258 publications have been published within this topic receiving 808079 citations. The topic is also known as: 4-androsten-17beta-ol-3-one & 4-Androsten-3-one-17b-ol.

Androgen metabolism and mechanism of action in male pseudohermaphroditism: a study of testicular feminization.

Abstract: Publisher Summary This chapter discusses androgen metabolism and the mechanism of action in male pseudohermaphroditism. It has been found that testosterone is the major androgen secreted into the blood of most mammals and that this steroid has biological actions on many tissues. As animals with testicular feminization cannot respond to androgens in utero, tissues, such as prostate, Wolffian duct derivatives, and external genitalia, do not differentiate, and the tfm animal develops as a male pseudohermaphrodite. Male pseudohermaphroditism resembling testicular feminization also develops in animals that are deprived of androgens in utero by one of the several mechanisms, including castration, defective testosterone synthesis, and exposure to pharmacologic agents that either block androgen biosynthesis in the testis or androgen action at the end organ. When the gonaducts and external genitalia fail to undergo androgen-dependent differentiation in utero, they do not develop into a normal reproductive tract when subsequently exposed to large doses of androgens. Thus, certain tissues may acquire insensitivity to androgens during differentiation. The chapter also discusses ultrastructural examination of the interstitial area of vet rat testes that demonstrates increased peritubular connective tissue. The interstitial tissue consisted predominantly of fibroblasts and a few peritubular sheath cells.

Gonadotrophin-releasing Hormone Therapy in Hypogonadal Males with Hypothalamic or Pituitary Dysfunction

Abstract: Subcutaneous self-administration of synthetic gonadotrophin-releasing hormone 500 μg eight-hourly for up to one year by 12 male patients (five prepubertal) with clinical hypogonadism due to hypothalamic or pituitary disease resulted in the synthesis and continued release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). There was a rise in circulating androgen levels in all patients. Improvements in pubertal ratings were seen in some prepubertal patients. Potency returned in the adults and spermatogenesis was induced and maintained in the four patients who had received treatment for more than four months, total counts reaching between 7·8 and 432 × 106 spermatozoa. A fall in the FSH response to the releasing hormone occurred during spermatogenesis though LH was little affected. During the initial weeks of therapy FSH secretion usually occurred before that of LH though LH secretion was greater as treatment continued. FSH secretion also persisted for longer when treatment was stopped.

Neonatal exposure to potent and environmental oestrogens and abnormalities of the male reproductive system in the rat: evidence for importance of the androgen–oestrogen balance and assessment of the relevance to man

Abstract: The effects on reproductive tract development in male rats, of neonatal exposure to potent (reference) oestrogens, diethylstilboestrol (DES) and ethinyl oestradiol (EE), with those of two environmental oestrogens, octylphenol and hisphenol A were systematically compared. Other treatments, such as administration of a gonadotrophin-releasing hormone antagonist (GnRHa) or the anti-oestrogen tamoxifen or the anti-androgen flutamide, were used to aid interpretation of the pathways involved. All treatments were administered in the neonatal period before onset of puberty. The cellular sites of expression of androgen receptors (AR) and of oestrogen receptor-alpha (ERalpha) and ERbeta were also established throughout development of the reproductive system. The main findings were as follows: (i) all cell types that express AR also express one or both ERs at all stages of development; (ii) Sertoli cell expression of ERbeta occurs considerably earlier in development than does expression of AR; (iii) most germ cells, including fetal gonocytes, express ERbeta but not AR; (iv) treatment with high, but not low, doses of potent oestrogens such as DES and EE, induces widespread structural and cellular abnormalities of the testis and reproductive tract before puberty; (v) the latter changes are associated with loss of immunoexpression of AR in all affected tissues and a reduction in Leydig cell volume per testis; (vi) none of the effects in (iv) and (v) can be duplicated by treating with high-dose octylphenol or bisphenol A; (vi) none of the reproductive tract changes in (iv) and (v) can be induced by simply suppressing androgen production (GnRHa treatment) or action (flutamide treatment); and (vii) the adverse changes induced by high-dose DES (iv and v) can be largely prevented by co-administration of testosterone. Thus, it is suggested that many of the adverse changes to the testis and reproductive tract induced by exposure to oestrogens result from a combination of high oestrogen and low androgen action. High oestrogen action or low androgen action on their own are unable to induce the same changes.

Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.

Abstract: We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation. When the pure (nonaromatizable) androgen, 5-alpha-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition of LH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-17 beta did not change significantly, but serum 5 alpha-dihydrotestosterone concentrations increased approximately two- to threefold, with a corresponding increase in levels of its major metabolite, 5 alpha-androstan-3 alpha, 17 beta-diol. In separate experiments, the infusion of estradiol-17 beta at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-17 beta levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions. Our observations indicate that, despite the continuous infusion of a dosage of 5 alpha-dihydrotestosterone that significantly suppresses LH pulse frequency, co-administration of an opiate-receptor antagonist effectively reinstates LH pulse frequency to control levels. Moreover, during the infusion of a suppressive dose of estradiol-17 beta, opiate receptor blockade significantly augments LH pulse frequency and increases LH peak amplitude to control levels. Thus, the present studies in normal men demonstrate for the first time that the selective inhibitory action of a pure androgen on LH pulse frequency is effectively antagonized by opiate-receptor blockade. This pivotal observation indicates that opiatergic and androgen-dependent mechanisms specifically and coordinately control the hypothalamic pulse generator for gonadotropin-releasing hormone (GnRH)