Testosterone metabolites do not participate in the control of hypothalamic LH-releasing hormone

Abstract

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)

Testosterone and the control of hypothalamic GnRH

“…The present data confirm, first of all, previous evidence of this (Zanisi et al 1986) and other laboratories (Shin & Howitt 1975, 1976Kalra et al 1977;Kalra & Kalra 1980;Bourguignon et al 1984) indicating that, in male rats, long-term (5 weeks) orchidectomy results in a decrease of intrahypothalamic GnRH stores. As mentioned in the Introduction, this decrease is due to an increased release of GnRH into the pituitary portal vessels (Eskay et al 1977;Sarkar & Fink 1980;Clayton & Catt 1981;Conne 1982;Limontaetal.…”

“…It is known that, in male rats, orchidectomy in¬ duces a significant decrease of the GnRH content of the mediobasal hypothalamus (MBH) (Shin & Howitt 1975, 1976Kalra et al 1977; Kalra & Kalra 1980;Bourguignon et al 1984;Zanisi et al 1986). This decrease is due to an increased release of GnRH into the pituitary portal vessels as shown by direct measurements (Eskay et al 1977;Sarkar & Fink 1980) …”

“…In a previous work from this laboratory, it was shown that 5a-androstan-17ß-ol-3-one (dihydrotestosterone, DHT), 5a-androstane-3a, 17ß-diol) (3a-diol), 5a-androstane-3ß,17ß-diol (3ß-diol (three metabolites which are formed from testos¬ terone in the brain and in the anterior pituitary through the process of 5ct-reduction, and which are believed to represent the 'active' form of the androgenic hormone in the control of LH secre¬ tion) (see Martini 1982) are unable to mimic the effect of testosterone on the re-establishment of a normal hypothalamic GnRH content in orchidectomized animals (Zanisi et al 1986). In the same study it was also demonstrated that administration of estradiol benzoate causes a significant increase, in the male rat, in the intrahypothalamic stores of GnRH, when these have been reduced by castra¬ tion (Zanisi et al 1986). It is known that, in the central nervous system (especially in the hypo¬ thalamus and in the limbic structures), testoster¬ one may be aromatized to yield estradiol-17ß and estrone (see Martini 1982).…”

Metabolism of androgens in rat pituitary gland and hypothalamus: Catabolism of dihydrotestosterone or transformation of androgen signal?

“…However, this problem is still poorly understood. Some authors reported that 5o~-reduction of testosterone is not necessary for the regulation of gonadotropin secretion in rats [43,68].…”

“…Obviously, it is important whether or not androgen metabolites act at the level of rat pituitary gland or hypothalamus, or they affect both these structures. Some authors assume that androgens exert their effects at the level of the pituitary gland [35,68], while others believe that these hormones affect the hypothalamus [28,29]. It was also reported that androgens regulate gonadotropic functions by acting simultaneously on the pituitary gland and hypothalamus [27,34].…”