Stimulation of Spermatocyte Development in Prepubertal Rats by the Sertoli Cell Steroid, 3α-Hydroxy-4-Pregnen-20-One1

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Abstract
The effect of 37a-hydroxy-4-pregnen-3-one, (3HP), a Sertoli cell steroid, on spermatogenesis was examained in normal and gonadotropin-suppressed rats, through s.c. as well as direct intratesticular injections. Early experiments employing normal prepubertal male rats indicate that 3HP, when administered at 65 .mu.g/100 g BW daily for 15 dyas, was capable of stimulating pachytene spermatocyte number to 149% of untreated control numbers. It was a interest to determine if this effect could be amplified in gonadotropin-suppressed animals. Neonatally estrogenized rats (500 .mu.g estradiol benzoate in 0.1 ml oil at 2 days) were treated on alternate days with 3HP (100 .mu.g/100 g BW) for 3 wk, starting at 7 days of age. This treatment significantly increased the number of spermatocytes per tubule cross section from 17.3 .+-. 1.9 (in estradiol benzoate-only animals) to 47.1 .+-. 7.9 (p<0.01). In a similar study, 100 .mu.g/100 g BW of testosterone propionate could stimulate spermatocyte number to only 15.1 .+-. 2.2 cells per tubule cross section versus estradiol benzoate only numbers. A single intrastesticular injection of 3HP (2 ng in 2.0 .mu.l oil) in Methallibure-treated rats resulted in a significant increase in late pachytene spermatocyte numbers from 0.77 .+-. 0.12 in Methallibure only-treated rats to 1.70 .+-. 0.10 (p<0.001) cells per tubule cross section in 28-day-old rats. However, in this study, no other progesterone metabolite or androgenic steroid (testosterone, 5.alpha.-dihydrotestosterone, or 5.alpha.-androstan-3.alpha.,17.beta.-diol) tested was capable of this level of germ cell stimulation. In conclusion, 3HP appears to have a direct effect on germ cell development within the testis at levels much lower than those shown to be effective for androgens. It does not appear that this effect is mediated through the conversion of 3HP to any C21 or C19 steroids, and appears to be the first report of a Sertoli cell steroid with a possible role in the process of mammalian spermatogenesis.