Testicular modulation of luteinizing hormone response to gonadotropin-releasing hormone (GnRH)-agonist treatment.
We and others have observed that the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to chronic gonadotropin-releasing hormone-agonist (GnRH-A) treatment is substantially different in normal compared to hypogonadal males. These data suggested that products of the testes determine the gonadotropin response to GnRH-A. The present studies were designed to determine whether this effect is mediated by products of the interstitial (steroids) or the tubular compartment. To create experimental states with selective impairment of interstitial, tubular, or both compartments, 100 male sexually mature Wistar rats were divided into five groups: I, intact; II, castrated; III, castrated with 20-mm testosterone (T) implants; IV, bilaterally cryptorchid; and V, ketoconazole-treated animals. Cryptorchid animals have been shown to have impairment of tubular function while ketoconazole inhibits T biosynthesis. Each of the 5 groups was divided into 2 subgroups to receive daily injections of either saline or 1 microgram of a potent GnRH agonist, D-leu6 des-Gly10 GnRH N-ethylamide, for 4 wk. Unlike the intact animals, which showed an elevation of basal serum LH concentration after 4 wk of GnRH-A treatment, the castrated animals showed significant suppression below baseline. Animals with preferential impairment of tubular function (cryptorchid and castrated + T) also showed significant suppression of LH after GnRH-A treatment. However, the ketoconazole-treated animals (with inhibition of T biosynthesis and intact tubular function), behaved similarly to intact animals and demonstrated an elevation of LH after GnRH-A treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003456:Cryptorchidism / Q000503:physiopathology; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D007006:Hypogonadism / Q000503:physiopathology; D007654:Ketoconazole / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology / Q000502:physiology
D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013007:Growth Hormone-Releasing Hormone; D007654:Ketoconazole