Delay in Some Aspects of the Sexual Maturation of the Male Rat Induced by Androstenedione1

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Abstract
The high androstenedione (.DELTA.4) to testosterone (T) ratios found in the serum of prepubertal male rats may prevent the maturation of the gonadotropin negative feedback centers. Silastic capsules (100 mm2 surface area) containing crystalline .DELTA.4 were implanted s.c. into 26 day old male rats to maintain a high blood .DELTA.4 level regardless of changes in testicular steroid secretion. Control rats received empty capsules. At 50 days, animals were castrated and their .DELTA.4 or blank capsules replaced with T filled capsules of 0 (empty), 25, 50, 100 or 150 mm2 surface area. Sham castrated animals retained their .DELTA.4 or blank capsules. On Day 54, rats were decapitated and serum was assayed for LH [lutropin], FSH [follitropin] and prolactin (PRL). There were no differences in gonadotropins between .DELTA.4 and blank capsule treated animals either after castration with no T replacement or after sham surgery. In rats pretreated with .DELTA.4 a 25 mm2 T capsule resulted in a significant LH suppression compared with values in castrated rats. The 25 mm2 T capsule was ineffective in rats pretreated with empty capsules; in this group a 50 mm2 capsule was necessary to maintain serum LH levels lower than those of castrated controls. The FSH negative feedback centers appeared unaffected by .DELTA.4 pretreatment. Prostates in rats pretreated with .DELTA.4 showed an enhanced sensitivity to T, a response typical of the immature rat, whereas seminal vesicles showed no effect of treatment. No differences in PRL that could account for these results were observed. Removal of .DELTA.4 capsules on Day 45 led to an apparent maturation of the LH negative feedback center when tested at 50 days. In this experiment, neither a 25 nor a 50 mm2 T capsule altered the castration-induced LH increase. Control rats (.DELTA.4 capsule manipulated but left in at 45 days) required a 50 mm2 capsule for LH suppression. .DELTA.4 was ineffective in modifying the response to T after maturational changes had occurred. Implantation of a .DELTA.4 capsule at the time of castration of 26 day old males prevented the maturation of the LH feedback center that had occurred 5 days later in control rats. The pituitary response of .DELTA.4 pretreated rats to a single LHRH [luliberin] injection did not show the enhancement by T that is typical of the immature male. In response to multiple LHRH injections, animals pretreated with .DELTA.4 did not show the selfpriming effect that is characteristic of the mature male rat. Prepubertal treatment with .DELTA.4 apparently prevents the maturation of the LH negative feedback system, the prostate and the LHRH selfpriming effect. .DELTA.4 does not appear to alter the maturation of the FSH feedback system, the seminal vesicles or the T potentiation sensitivity to LHRH.