Suppression Of Androgen Production Research Articles

Suppression of androgen production by D-tryptophan-6-luteinizing hormone-releasing hormone in man.

Four male transsexual subjects were given a superactive luteinizing hormone-releasing hormone (LHRH) analogue, D-tryptophan-6-LHRH at daily doses of 100 micrograms for 3--6 mo. A decrease in beard growth, acne, and erectile potency was noted; the latter was documented objectively with the recordings of nocturnal penile tumescence episodes. Plasma testosterone and dihydrotestosterone levels fell to castrate values; basal prolactin and luteinizing hormone levels showed a small decline, whereas the acutely releasable luteinizing hormone was significantly suppressed. A rise of plasma testosterone from castrate to normal levels was demonstrable with the use of human chorionic gonadotropin. Discontinuation of treatment led to a normalization of erectile potency and plasma testosterone. The suppression of Leydig cell function by D-tryptophan-6-LHRH might have wide application in reproductive biology and in endocrine-dependent neoplasia (where it could replace surgical castration).

Rapid interaction between luteinizing hormone and isolated rabbit follicles.

The rapidity of binding of LH to rabbit ovarian follicles was examined using androgen production as the endpoint. Incubations were carried out for about 8 h with medium being changed every 15 min except during the periods when follicles were exposed to LH and/or anti-LH and subsequent washing. Exposure of follicles to LH for 1 s followed by washing in (a) LH-free medium, (b) pure anti-LH or (c) diluted anti-LH, failed to inhibit androgen production which persisted for more than 2 h. Simultaneous addition of anti-LH and LH to the medium before incubation with follicles completely inhibited the response though it could be elicited from the same follicles when LH was added later. These data suggest that the binding of LH to follicular receptors is a rapid process and that either the LH-receptor complex is very stable or that LH initiates a series of reactions which are independent of the presence of hormone.

Influence of immunization with luteinizing hormone upon the anterior pituitary-gonad system of rats and rabbits, with special reference to histological changes and biosynthesis of luteinizing hormone and steroids.

Active immunization of rats and rabbits with ovine luteinizing hormone (NIH-LH- S7) caused a marked atrophy of the testis, seminal vesicle and prostate, and hypertrophy of the anterior pituitary and adrenal glands. Inhibition of spermatogenesis and of the androgen-producing activity of the testis was observed, while the proliferation and enlargement of the basophilic cells with increased PAS-positive granules in both central and peripheral regions of the anterior pituitary gland were apparent histologically. A radioimmunochemical study on the de novo biosynthesis of LH in the anterior pituitaries of these immunized animals showed a marked increase of amino acid incorporation into the LH fraction. Passive immunization of rats with the rat anti-ovine LH-antiserum, or castration, showed similar changes, while no significant changes were observed in the animals receiving LH without adjuvant. These results suggested that immunization of the animals with ovine LH caused the production of anti-LH-antibody, inhibiting the action of the endogenous LH of the animals, which resulted in the inhibition of androgen production in the testis. The deficiency of androgens caused proliferation of gonadotrophs and increased production of LH in the anterior pituitary gland, similar to the situation after castration. (Endocrinology79: 477, 1966)