Estradiol stimulates progesterone synthesis in hypothalamic astrocyte cultures.

The brain synthesizes steroids de novo, especially progesterone. Recently estradiol has been shown to stimulate progesterone synthesis in the hypothalamus and enriched astrocyte cultures derived from neonatal cortex. Estradiol-induced hypothalamic progesterone has been implicated in the control of the LH surge.

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).

Estrogen induces de novo progesterone synthesis in astrocytes.

The brain is an established target for peripheral steroids, but also expresses steroidogenic enzymes and is capable of de novo 'sex' steroid synthesis (neurosteroidogenesis) independent of peripheral steroidogenic organs. In adrenalectomized and ovariectomized rats that do not have peripheral sources of steroids, estrogen treatment increased progesterone levels specifically in the hypothalamus, indicating that estrogen stimulates progesterone neurosteroidogenesis. Recent studies have demonstrated that specific cell types preferentially secrete specific steroids, and that astrocytes are the primary progesterone synthesizing cells in the nervous system.

The luteinizing hormone surge is preceded by an estrogen-induced increase of hypothalamic progesterone in ovariectomized and adrenalectomized rats.

As circulating estrogen levels rise on the afternoon of proestrus, they stimulate the hypothalamo-pituitary axis. This estrogen positive feedback is pivotal to stimulate the luteinizing hormone (LH) surge required for ovulation and luteinization of ovarian follicles. In addition to estrogen, pre-LH surge progesterone is critical for an LH surge as was demonstrated by blocking progesterone synthesis.

Site-specific decrease of progesterone receptor mRNA expression in the hypothalamus of middle-aged persistently estrus rats.

Middle-aged females gradually become acyclic and spontaneously develop a persistently estrus (PE) state. PE rats, acyclic for 30 days (early PE), are unresponsive to the positive feedback action of estrogen, but respond to a progesterone challenge with a luteinizing hormone (LH) surge and ovulation; unlike long-term PE rats, acyclic for 90 days, neither estrogen nor estrogen plus progesterone will elicit an LH surge [10th International Congress of Endocrinology, San Francisco, P3 (1996) 1061]. We hypothesize that the PE state may develop due to a diminished level of estrogen-induced progesterone receptor (PR) expression in the hypothalamus that prevents progesterone from stimulating LH regulating circuits.