Effects of Castration and Testosterone on the Pituitary and Adrenal Responses of the Newborn Rat to Ether Inhalation

Abstract

In 8-day-old rat newborns, the pituitary response to 2 min of ether inhalation was noted to vary according to sex. Plasma ACTH levels were similarly increased in males and females at the end of ether exposure; however, during the following 30 min, ACTH levels were always higher in females than in males. In order to verify that the putative masculinization of some neuroendocrine pathways involved in the pituitary response to ether stress was the result of the transitory surge of testosterone at birth, fetuses at term were delivered by cesarean section and thereafter immediately castrated or sham-castrated under cold anesthesia (males), injected with testosterone heptylate (1 mg s.c.) or olive oil used as solvent (females) before being put in the care of a nurse. The rise in plasma testosterone levels during the 1st h after birth was prevented or stopped in males put at 2 °C. At the 8th postnatal day, the newborns were subjected to 2 min of ether inhalation; they were sacrificed either just, before or after the end (0 and 30 min) of the stress procedure. Plasma immunoreactive ACTH level and adrenal corticosterone content were measured. The pituitary response, shown by the ACTH increase, in castrated or sham-castrated males and testosterone-injected females was similar to that of intact males but very different from that observed in olive-oil-injected or intact females. The rise in adrenal corticosterone content 30 min after ether inhalation was greater in intact and olive-oil-injected females than in testosterone-injected ones or in males; adrenal response was well correlated with the maintenance of ACTH release in the former and the decrease following transitory surge in the latter. Present data suggest – in the male, prenatal differentiation of the neuroendocrine pathways involved in the pattern of ACTH release in response to ether inhalation – in the female, the existence of androgen-sensitive structures in early postnatal life.

ACTH secretion from isolated hypophysial anterior lobes of male and female newborn rats: effects of corticotrophin-releasing factor, arginine vasopressin and oxytocin alone or in combination

“…Testosterone-injected females show a smaller ACTH response to ether stress than intact females on day 8 postpartum and the secretion of ACTH is simi¬ lar to that observed in males (Hary et al 1986). In the present study, the adenohypophysis of the testo¬ sterone-injected females did not show in-vitro potentiation by oxytocin of the response to rCRF; the response was very different from that observed in olive oil-injected females, but was similar to that observed in intact males.…”

“…The former data could suggest that differences between sexes in AVP and/or oxytocin release or AVP and/or oxytocin effects on the adenohypophysis could be involved in the sex-related differences in the responsiveness of the 8-day-old rat pituitary gland to stress. However, the sex difference for response to ether inhalation was abolished when newborn females delivered by Caesarean section were injected with testosterone at the time of birth (Hary et al 1986). In contrast, castration of male pups at birth did not affect the stress-induced ACTH release (Hary et al 1986).…”

“…However, the sex difference for response to ether inhalation was abolished when newborn females delivered by Caesarean section were injected with testosterone at the time of birth (Hary et al 1986). In contrast, castration of male pups at birth did not affect the stress-induced ACTH release (Hary et al 1986). These results sug¬ gest a prenatal sexual differentiation of neuroendo¬ crine pathways involved in the pattern of ACTH release in response to ether inhalation.…”

A direct androgenic involvement in the expression of human corticotropin-releasing hormone

“…[67][68][69] In rodents, early androgen exposure disrupts feminine behavior, gonadotropin release and neuroanatomical sexual differentiation 70,71 and suppresses the HPA axis, 72 whereas in human, prenatal estrogen administration, that is, by DES, was found to increase the risk of affective disorders. 73,74 These observations, together with our present data raise the possibility that androgens may also play a role, either via direct or indirect effects, in prenatal programming and in activity of the adult CRH neurons, and may thus be involved in the sex differences in the stress response and in the risk for mood disorders.…”

Reduction in Testicular Function in Rats

“…Indeed, in the first minutes after birth, a transitory surge in plasma testosterone [3,[11][12][13][14] has been found to be assoReceived: December 28, 1988 Accepted after revision: July 27, 1989 ciated with a release of LH [3,15] and a transient increase in gonadotropin-releasing hormone (GnRH or LH-releasing hor mone) content of the hypothalamus [16]. This surge in plasma testosterone was absent in male rats gonadectomized at birth [3,11] or in those with a reduced body temperature [ 17,18]. These results are consistent with an increased activity of the hypothalamo-pituitary-testicular axis at birth.…”