Agonadal Subjects Research Articles

Androgens in the feedback regulation of gonadotropin secretion in men: effects of administration of dihydrotestosterone to eugonadal and agonadal subjects and of spironolactone to eugonadal subjects.

To study the role of androgens in the feedback regulation of gonadotropin secretion, we measured the effects of administration of dihydrotestosterone undecanoate (DHTU) and of spironolactone. Basal and LRH stimulated LH/FSH levels were determined in: Six eugonadal men, before and after six weeks' DHTU 120 mg/day. Six agonadal subjects after 12 weeks' DHTU 120 mg/day. The results of B were compared to those of Six agonadal subjects without sex steroid treatment. Six eugonadal subjects were studied before and after six weeks' administration of spironolactone. In the two groups of eugonadal subjects, administration of either dihydrotestosterone or spironolactone had no effect on basal and LRH-stimulated gonadotropin levels. A clear but modest suppression was observed in agonadal subjects. Possibly DHT exerts some suppressive effect on gonadotropin secretion in the absence of other testicular products (estradiol, testosterone, inhibin), known to play a role in the negative feedback regulation. From these data it seems unlikely that in the eugonadal male circulating DHT has an important role in the feedback regulation of gonadotropin secretion.

Estrogens in the feedback regulation of gonadotropin secretion in men: effects of administration of estrogen to agonadal subjects and the antiestrogen tamoxifen and the aromatase inhibitor delta'-testolactone to eugonadal subjects.

To elucidate the specific role of estrogens in the feedback regulation of gonadotropin secretion in men, basal and LRH-stimulated gonadotropin levels were studied in: Six agonadal subjects Six agonadal subjects continuously treated with 50 micrograms ethinylestradiol Six eugonadal subjects, treated with the aromatase inhibitor delta'-testolactone, which induced a reduction of estrogen levels, independently of testosterone. Further, to determine whether estrogens exert differential effects in time on LH and FSH secretion, the anti-estrogen tamoxifen was administered to: Six eugonadal subjects for two weeks and Six eugonadal subjects for six weeks. It was found that estrogens have a strong suppressive effect on both LH and FSH secretion. However, changes in estrogen levels and blocking of estrogen receptors are followed more rapidly by FSH than LH. Estrogens affect LRH-induced LH release more than basal LH levels; basal and LRH-stimulated FSH are approximately equally influenced. Basal and LRH-induced LH secretion are known to be more dependent upon previous LRH stimulation than FSH secretion. Since FSH followed changes of estrogens more rapidly than LH did, we postulate that the negative feedback action of estrogens on: LH secretion is predominantly exerted at the level of the hypothalamus, through inhibition of LRH secretion FSH secretion predominantly at the level of the pituitary through a direct action on the gonadotroph.

Sex steroids and pulsatile luteinizing hormone release in men. Studies in estrogen-treated agonadal subjects and eugonadal subjects treated with a novel nonsteroidal antiandrogen.

This study evaluated the effects of estrogens and androgens on LH pulse frequency and amplitude in male subjects. To assess the role of estrogens we compared the serum LH pulse frequency and amplitude between 3 groups: 8 agonadal subjects receiving no steroid treatment; 6 agonadal subjects continuously treated with 50 micrograms ethinylestradiol/day; and 17 eugonadal men. Mean serum LH levels and LH pulse amplitude were significantly lower in the agonadal subjects receiving estrogens (14.8 +/- 5.4 (SD) U/L and 4.1 +/- 1.5 U/L, respectively) than in the group of agonadal subjects not receiving sex steroid treatment (35.7 +/- 8.4 U/L and 7.3 +/- 2.0 U/L, respectively). The mean LH pulse frequency was 7.1 +/- 1.5/7 h in the group not receiving sex steroid treatment and 6.0 +/- 1.4/7 h in the group receiving estrogens (P NS). The LH pulse frequency in the eugonadal men (3.8 +/- 1.3/7 h) was significantly lower than the frequency in both groups of agonadal subjects. The LH pulse amplitude was of the same magnitude in the estrogen-treated agonadal subjects and in eugonadal men (4.1 +/- 1.5 U/L and 3.5 +/- 1.2 U/L, respectively). The role of androgens was studied in 15 eugonadal male subjects (who presented for female role reassignment) by determining the effects of a novel nonsteroidal androgen receptor blocker, Anandron, on basal and LH-releasing hormone (LHRH)-stimulated serum LH/FSH levels; LH pulse frequency and amplitude; sex steroid and sex hormone-binding globulin levels; and serum PRL levels during an 8-week period. Basal and LHRH-stimulated LH levels and testosterone rose progressively during the first 6 weeks and reached a plateau thereafter, while estradiol levels continued to increase somewhat. The LH pulse amplitude and frequency had increased after 6 weeks (3.1 +/- 0.6 vs. 4.5 +/- 1.2 U/L and 4.4 +/- 2.4 vs. 6.6 +/- 1.1 pulses/7 h, respectively). Basal FSH levels were not affected while LHRH-stimulated FSH levels progressively decreased from 2 to 6 weeks, after which they did not change. Along with the rise of estradiol levels an increase of sex hormone-binding globulin and PRL levels occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

Testosterone propionate treatment of an XY gonadal dysgenetic chacma baboon

Behavioral studies of an XY gonadal dysgenetic chacma baboon prior to and during testosterone propionate treatment were carried out. The orchidectomized dysgenetic individual, two intact males, a castrate male, and two ovariectomized females were pair-tested with a group of eight ovariectomized stimulus females prior to and during their treatment with estradiol benzoate. Three test series were carried out. One series occurred prior to any treatment of the agonadal focal subject animals. During this series it was only the intact males who showed behavior change during their testing with the estrogen treated females. A second test series occurred after a month of daily testosterone propionate injections (1 mg/kg/day) had been given to the four agonadal subjects. During this test series the castrate male ejaculated once with one of the estrogen-treated females. All of the treated subjects showed increases in their frequency of yawning. Upon completion of this test series the androgen dosage was increased (2 mg/kg/day) and 2 weeks later a third test series was carried out. During this series the castrate male ejaculated with five of his eight estrogen-treated partners. The yawning of all the treated subjects continued. As had been the case in the second series the XY gonadal dysgenetic individual continued to behave as did the ovariectomized females. None of these animals showed any increase in any measure of male sexual behavior. This study establishes the fact that a genetic male primate deprived of in utero exposure to testicular hormones will go on to develop as a normal genetic female and will fail to exhibit increased levels of male sexual behavior during androgen treatment.

Somatostatin inhibits prolactin release from the lactotroph primed with oestrogen and cyproterone acetate in man.

The present study investigated the effect of administration of somatostatin (SRIF) on the release of prolactin in men. No effect was observed when SRIF was administered to eugonadal men. Release of prolactin was inhibited, however, when SRIF was administered to oestrogen-treated agonadal subjects (male-to-female trans-sexuals) and to an even greater degree when subjects had been pretreated with a combination of oestrogen and cyproterone acetate. This is consistent with findings in the rat. Thus in man, as in the rat, SRIF can inhibit prolactin secretion, but only after treatment with oestrogen.

Prolactin secretion in the human male is increased by endogenous oestrogens and decreased by exogenous/endogenous androgens.

There is evidence that prolactin may be involved in testicular steroidogenesis, and we have therefore investigated whether there is feedback regulation of androgens/oestrogens on prolactin secretion in the human male. To assess this we have measured basal and TRH-stimulated prolactin levels in: Six eugonadal men before and after 2 weeks' administration of the aromatase inhibitor delta'-testolactone, which led to a fall in oestradiol levels with unchanged levels of testosterone. In these patients, prolactin levels decreased. Six eugonadal subjects before and after 6 weeks' administration of dihydrotestosterone undecanoate. In these subjects, prolactin levels decreased. Six agonadal subjects, tested after 12 weeks' treatment with dihydrotestosterone undecanoate and compared to: Six agonadal subjects who received no sex steroid treatment. Again, it was found that dihydrotestosterone treatment decreased prolactin levels in patients from Group C. Six eugonadal subjects were also studied before and after 6 weeks' administration of the androgen receptor antagonist, spironolactone, and this treatment increased Prl secretion. It is concluded that in the human male, endogenous oestrogens increase prolactin secretion whilst exogenous/endogenous androgens decrease prolactin secretion.

The effects of ovariectomy and estrogen treatment on the dopamine inhibition of gonadotropin and prolactin release.

The suppressive action of dopamine (DA) on circulating gonadotropin and PRL levels is found to be positively correlated with their basal serum concentrations. Thus, DA inhibition is greater in ovariectomized (agonadal) women than in normal women on day 2 of their menstrual cycles, and the reverse is observed for PRL. Pretreatment of agonadal subjects with estrogen lowers the basal levels of LH and FSH and thereby proportionately decreases the suppressive effects of DA. Estrogen treatment elevates the basal level of PRL in agonadal subjects and also the PRL-inhibiting effect of DA. These findings indicate that castration and estrogen treatment significantly influence the inhibitory effect of DA on gonadotropin and PRL release.

80: PRENATAL LH-DEFICIENCY AS POSSIBLE CAUSE OF MALE PSEUDOHERM-APHRODITISM, HYPOSPADIAS, HYPOGENITALISM AND CRYPTORCHIDISM

Some boys with gonadotropin (Gn)deficiency have hypogenitalism (very small penis). In some patients with cryptorchidism LHRH stimulated LH is low while FSH is high or normal (our experience and Canlorbe et al. 1974). The following two observations suggest that fetal LH is not only important for genital growth and testicular descent, but also for genital differentiation. Patient 1 is a girl aged 10 with ambiguous genitalia, XY karyotype, inguinal testes and no pregnantriol and testosterone response to HCG. LHRH stimulated LH was low and remained low 1 week and 6 months after bilateral castration while FSH increased to very high levels as seen in agonadal subjects, Patient 2 is a male adolescent with mild hypospadias,bilateral cryptorchidism, XY karyotype and Gn deficiency with anosmia (Kallmann syndrome).- In the male rabbit, fetal Gn deficiency produced by decapitation prior to or during genital differentiation results in female genitalia or hypospadias (Jost 1951). So far it has been assumed that in the human fetus, testosterone secreted by the Leydig cells and responsible for the differentiation of the male genitalia is not controlled by the fetal Gn as in the rabbit but rather by HCG, and that the fetal Gn take over their control of testicular function only after the period of genital differentiation. The experience presented here suggests that this concept may be wrong and that prenatal hypothalamo-pitultary disorders with LH deficiency may cause male pseudohermaphroditism, hypospadias, hypogenitalism and cryptorchidism, depending on the severity and timing of the deficiency.

Serum gonadotropin in concentrations in agonadal children and adults.

ABSTRACT Serum FSH concentrations were elevated above the age-specific normal range in all of 51 agonadal subjects ranging in age from 2 months to 22 yr. Serum LH levels were also elevated in most of these subjects. Although serum gonadotropin concentrations were above normal in the 18 infants and children, levels were significantly higher in subjects who were above the normal age of puberty. No significant differences in serum testosterone and estradiol concentration could be demonstrated between castrate and normal children. The data provide further evidence for a dynamic hypothalamic-pituitary-gonadal feedback relationship during childhood. The identity of the gonadal product responsible for the feedback inhibition is not clear. The further increment in serum gonadotropin concentrations after the normal age of puberty in agonadal subjects suggests that the changes in the hypothalamic “gonadostat” during normal puberty may occur in the absence of a functional gonad.