Testosterone metabolites do not participate in the control of hypothalamic LH-releasing hormone.
To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormone (LHRH) in orchidectomized rats might be explained by the conversion of the hormone into either its 5 alpha-reduced or oestrogenic metabolites, testosterone, 5 alpha-androstan-17 beta-ol-3-one (DHT), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-diol) and 5 alpha-androstane-3 beta,17 beta-diol (3 beta-diol) (2 mg/rat per day for 6 days) and oestradiol (0.1, 0.5, 1.0 and 5.0 micrograms/rat per day for 6 days) were injected into castrated male rats. After 6 days the rats were killed and serum LH levels and intrahypothalamic LHRH stores measured using specific radioimmunoassay procedures. Testosterone and its 5 alpha-reduced metabolites were used in either the free alcohol or the propionate form (dipropionates in the case of the diols); oestradiol was used as oestradiol-17 beta or in the benzoate form. Treatment with testosterone, DHT, 3 alpha-diol and 3 beta-diol resulted in a significant decrease in serum LH levels; all the 5 alpha-reduced testosterone derivatives were more effective than testosterone in this respect. Testosterone and DHT propionates suppressed LH release following orchidectomy totally; 3 alpha-diol and 3 beta-diol dipropionates were less effective. Testosterone increased intrahypothalamic LHRH stores, this effect being much higher after testosterone propionate, i.e. when intrahypothalamic LHRH stores were restored to pre-castration levels. None of the 5 alpha-reduced steroids was capable of modifying the low intrahypothalamic levels of LHRH found following orchidectomy; only 3 alpha-diol dipropionate exhibited some activity, but this was much lower than that of testosterone propionate. Oestradiol-17 beta was totally ineffective in decreasing serum LH in orchidectomized animals; in contrast, oestradiol benzoate progressively decreased serum LH.(ABSTRACT TRUNCATED AT 250 WORDS)
D015113:Androstane-3,17-diol / Q000494:pharmacology; D000818:Animals; D013196:Dihydrotestosterone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D009919:Orchiectomy; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013739:Testosterone / Q000502:physiology*
D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone