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 (E 2 ), both alone and with progesterone (P 4 ), in middle-aged, early persistent-estrous (PE) female rats that had become PE within 35 days. In addition, we also assessed the effect of P 4 on the mating-induced gonadotropin surges in these acyclic animals. Early PE rats were ovariectomized and received E 2 implants (Day 0). On Day 4, an s.c. injection of P 4 (0.5 mg/ 100 g body weight) at 1200 h markedly increased plasma P 4 and elicited both LH and FSH surges, whereas vehicle-treated controls displayed no rise in P 4 or gonadotropins. This observation confirms that at middle age, female rats no longer respond to the positive-feedback stimulation of E 2 on gonadotropin surges whenever the estrous cyclicity ceases. As PE continued, such a surge-inducing action of E 2 plus P 4 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 P 4 from the adrenal along with small gonadotropin surges. The amplitude of these mating-induced gonadotropin surges was enhanced by supplementation with exogenous P 4 in early PE rats. Our findings indicate that during the early phase of PE, the surge-inducing action of E 2 and P 4 remains intact but deteriorates as PE continues. Thus, a deficiency in P 4 secretion during aging may contribute to the diminished gonadotropin surge response in the hypothalamic-pituitary axis and the subsequent cessation of estrous cyclicity.