Temporal Changes Occur in the Neuroendocrine Control of Gonadotropin Secretion in Aging Female Rats: Role of Progesterone

The present study examined the gonadotropin surge-inducing actions of estradiol (E2), both alone and with progesterone (P4), in middle-aged, early persistent-estrous (PE) female rats that had become PE within 35 days. In addition, we also assessed the effect of P4 on the mating-induced gonadotropin surges in these acyclic animals. Early PE rats were ovariectomized and received E2 implants (Day 0). On Day 4, an s.c. injection of P4 (0.5 mg/ 100 g body weight) at 1200 h markedly increased plasma P4 and elicited both LH and FSH surges, whereas vehicle-treated controls displayed no rise in P4 or gonadotropins. This observation confirms that at middle age, female rats no longer respond to the positive-feedback stimulation of E2 on gonadotropin surges whenever the estrous cyclicity ceases. As PE continued, such a surge-inducing action of E2 plus P4 became diminished after 75 days of PE and disappeared thereafter. When caged with males, vehicle-treated early PE rats display a mating-induced increase in P4 from the adrenal along with small gonadotropin surges. The amplitude of these matinginduced gonadotropin surges was enhanced by supplementation with exogenous P4 in early PE rats. Our findings indicate that during the early phase of PE, the surge-inducing action of E2 and P4 remains intact but deteriorates as PE continues. Thus, a deficiency in P4 secretion during aging may contribute to the diminished gonadotropin surge response in the hypothalamicpituitary axis and the subsequent cessation of estrous cyclicity.