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.

Adult↗

PubMedDate not supplied

Interaction of inhibin and estrogens on basal and LRH-stimulated gonadotropin levels.

In order to study the action of estrogens and inhibin and their interaction with gonadotropin secretion in men, we measured basal and LRH-stimulated gonadotropin secretion before and after six weeks' administration of tamoxifen in two groups of men. A) Six men with impaired spermatogenesis with basal levels of FSH, LH, testosterone and estradiol within the range of reference values in our laboratory. B) Six men with severely impaired spermatogenesis. LH, testosterone and estradiol levels were within reference values, whereas FSH was at least 100% above the upper limit of reference values. Mean testosterone and estradiol levels were not different in either groups. Inhibin levels were presumed to be normal in group A and decreased in group B. Although within reference values, basal LH levels in group B were slightly but significantly higher than in group A. The response of LH to LRH in group B exceeded that of group A. This suggests that inhibin has a slightly inhibitory effect on basal LH and even more so on LRH-induced LH secretion. After tamoxifen administration basal FSH levels rose far more in group B than in group A. The LRH-induced LH release increased in both groups, the LRH-stimulated FSH release, however, increased only in group A. We conclude that estrogens and inhibin have a strongly synergistic negative feedback action on basal FSH secretion, and to a limited extent on basal LH secretion. In the presumed presence of inhibin (group A) the FSH additionally synthesized through the action of anti-estrogens, can be released by LRH administration, whereas FSH is probably spontaneously released in the presumed deficiency of inhibin (group B). With LH this phenomenon is less obvious.

Adult↗

PubMedDate not supplied

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.

Adult↗