SUPPRESSION OF LUTEINIZING HORMONE SECRETION IN MALE RATS BY 5α-Androstan-17β-Ol-3-One (DIHYDROTESTOSTERONE) PROPIONATE

Abstract

Dihydrotestosterone propionate (DHTP) administered to intact, 25-day-old rats over a period of 6 days causes a significant decrease in testicular weight. Concurrent administration of gonadotrophic hormone prevents this decrease in testicular weight (Feder, 1971). Similarly, Beyer, Moral\l=i'\& Cruz (1971) demonstrated that DHTP blocked ovarian compensatory hypertrophy in female rats. These findings and earlier reports (Bottomley & Folley, 1938; Dorfman & Kind, 1966) suggested that dihydrotestosterone suppressed secretion of gonadotrophic hormones. However, direct measurements of plasma concentrations of the gonadotrophins after DHTP treatment of young rats were unavailable. This report offers quantitative data on systemic plasma concentrations of luteinizing hormone (LH) in young male rats treated with DHTP. A previously described radioimmunoassay method was used for LH measurement (Niswender, Midgley, Monroe & Reichert, 1968;Naftolin & Corker, 1971).In one experiment intact Sprague\p=m-\Dawley male rats were injected daily with 125 \g=m\gDHTP, 375 \g=m\g DHTP, 125 \g=m\g testosterone propionate (TP) or 0\m=.\3ml sesame oil vehicle. The subcutaneous injections were given on days 25 to 30, inclusive, of life. Another group of males was castrated (ether anaesthesia) on day 26. All animals were killed at 31 days of age (barbiturate anaesthesia, Equithesin) and blood was drawn from the left ventricle into a heparinized syringe. The blood was immediately centrifuged under refrigeration and the plasma fraction frozen until assay. All assays were carried out under a double blind technique. Bleedings were carried out at 14.00 to 16.00 h (lights on 19.00 to 09.00 h), and testes and seminal vesicles were weighed after the rats were killed. The results are shown in Table 1. At the dosage used, DHTP was about as effective as TP in suppressing LH secretion; both produced significantly (P < 0-05) lower plasma concentrations of LH (Mann-Whitney U-test). These data are compatible with the evidence of Beyer, Gay & Jaffe (1972) that DHTP severely suppresses LH secretion in adult female rats.In a second experiment the effects of acute treatment with DHTP were studied. Intact male rats, 29 days of age, were injected at 09.00 h with 125 µg DHTP, 125 µg TP or 0-1 ml sesame oil vehicle. The rats were killed and blood was withdrawn 6 h after injection of the steroid. The results in Table 2 show that even one treatment with DHTP is highly and consistently effective in suppressing LH secretion. Acute treatment with TP also inhibited LH secretion, but the results were somewhat less

Effect of Melatonin and Short Photoperiod on Δ4-Reductase Activity in Liver and Hypothalamus of the Hamster and the Rat

“…This implies that there may be species differences in the mechanisms through which melatonin and androgens affect gonadotrophin release in the two species. Studies, similar to those done with rats by other workers (Naftolin & Feder, 1973;Beyer et al 1972) should be undertaken to ascertain if dihydrotestosterone affects LH secretion in the same way in both species.…”

“…This finding is of particular interest since melatonin, when given to rats intraventricularly, suppresses serum levels of LH (Kamberi, Mical & Porter, 1970) and follicle-stimulating hormone (Kamberi et al 1971), and when placed in the median eminence of castrated male rats it decreased pituitary stores of LH (Fraschini et al 19686). Although both testosterone and dihydro¬ testosterone effectively suppress LH secretion in rats (Naftolin & Feder, 1973), observations by Beyer et al (1972) indicate that dihydrotestosterone is significantly more effective than testosterone in preventing an increase in serum LH levels in spayed rats. These studies suggest that the previously observed effects of melatonin on rat hypothalamus, that is, a lowering of serum and pituitary LH levels, may be at least partially brought about by the stimulatory effect of melatonin on A4-reductase.…”

Effect of Testosterone on Neuronal Refractory Periods, Sexual Behaviour and Luteinizing Hormone: A Comparison of Time-Courses

“…As testosterone propionate restores sexual behaviour in castrated rats (Young, 1961) and also reduces their LH levels (Brown-Grant, 1974), this neuronal change might be involved in the control of either response. In a previous paper we have shown that dihydrotestosterone propionate, an androgen that inhibits the release of LH as effectively as testosterone propionate itself (Naftolin & Feder, 1973), has no effect on these neurones (Kendrick & Drewett, 1980). In this paper we report studies on the time-course of changes in LH levels, sexual behaviour and neuronal refractory periods.…”

Lack of an Effect of Dihydrotestosterone on Serum Luteinizing Hormone in Neonatal Female Rats

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Testosterone and its ring A reduced metabolite, dihydrotestosterone (DHT), lower gonadotrophin concentrations in weaned rats (Swerdloff, Walsh & Odell, 1972;Naftolin & Feder, 1973). While neonatally administered testosterone causes anovulatory sterility in adult female rats, similar treatment with DHT has no apparent effect upon central neuroendocrine programming (Brown-Grant, Munck, Naftolin & Sherwood, 1971;Whalen & Luttge, 1971), which raises the question of whether DHT can suppress gonadotrophins in the neonatal rat.

In the first experiment, 5-day-old Sprague-Dawley-derived rats (Charles River Farms) were injected s.c. with 100 µg DHT propionate (DHTP), 100 µg testosterone propionate (TP, Eli Lilly & Co.) or the sesame oil diluent, and allowed to develop without further treatment.

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“…However, 6 h after injection the animals were exsanguinated by decapitation. In each group blood from four animals was pooled, centrifuged and assayed for serum luteinizing hormone (LH) as previously described (Naftolin & Feder, 1973). The error of the method was less than 5%.…”