Effects of Androgen Administered to Neonatal Male Rats on Hypophyseal Gonadotropin Content, Secretion and Response to LHRH at Adulthood

Abstract

Supraphysiologic doses (1.75-3.50 mg) of testosterone propionate (TP) administered to male rats on the day of birth and 24 h later resulted in markedly reduced serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in adult males castrated for 16 days. These effects diminished as androgen was injected on succeeding postnatal days. Since exogenous dihydrotestosterone and testosterone were similarly effective, aromatization to estrogen is not required to elicit these effects. No build-up of either gonadotropin occurred in the pituitaries of TP-treated animals; pituitary LH content was appreciably reduced, while FSH remained unchanged. These data imply that hypophyseal synthesis and secretion of gonadotropins are curtailed in adult castrated males who have been androgenized neonatally. Pituitaries of such neonatally treated animals, however, were capable of increased secretion of LH in response to a challenge of luteinizing hormone-releasing hormone. These findings are compatible with a model in which an androgen suppressible event occurs at a suprahypophyseal level, e.g., hypothalamus or higher brain centers, in the male rat during a restricted neonatal period, which is responsible for programming the development of mechanisms involved in accumulation and secretion of gonadotropins.

Effect of Neonatal Androgenization on the Testosterone Feedback Sensitivity in Adult Rats in Two Lighting Conditions

“…This is in accordance with the results of Feigelson and Linkie [18], who found the pituitary deficiency of LH being evident only after castration of the neonatally androgenized rats. It has been widely assumed that the site of action of androgenization is the hypothalamus [1,6,18].…”

“…This is in accordance with the results of Feigelson and Linkie [18], who found the pituitary deficiency of LH being evident only after castration of the neonatally androgenized rats. It has been widely assumed that the site of action of androgenization is the hypothalamus [1,6,18]. The pitu itary response to LHRH and the number and distribu tion of LHRH-producing cells has been found to be nor mal in neonatally androgenized rats [20,21], We found no difference in the hypothalamic LHRH content after androgenization, suggesting that the effects of androge nization are not due to changes in LHRH stores, which probably reflect LHRH synthesis.…”

“…However, in the neonatally androgenized rats only serum gonadotropins responded to testosterone injections in adulthood, while both pitu itary FSH and LH were unresponsive. This is in agree ment with the finding that neonatal androgenization pre vents the elevation of gonadotropins after castration in adulthood [11,18]: in both cases the gonadotropic axis is unable to respond to the changing testosterone concen tration. Our results give support to the concept that neo natal androgenization changes the testosterone response permanently in the adult rat [6,11].…”

“…Reports on neonatal androgenization-induced gonad otropic hormone changes in the adulthood of the male rat are contradictory: plasma levels of FSH and LH have been reported to rise [8,17], or there have been no changes in plasma or pituitary concentrations [ 18]. Ac cording to our results, neonatal androgenization pro duces no difference in either serum or pituitary concen trations of gonadotropins in periodical light.…”