Progesterone may act at hypothalamus and pituitary by way of enhancement of oestrogen retention

Abstract

PROGESTERONE injection given 24 h or more before ovulation inhibits the ovulatory cycle^1–5. There is evidence that progesterone can act directly on the hypothalamus^6–9 to block ovulation and on the pituitary to reduce pituitary sensitivity to luteinising releasing hormone^10,11. Steroid-sensitive target tissues including hypothalamus^12,13 and pituitary^14–16 contain a specific oestrogen retention mechanism of limited capacity. Oestrogen-regulated events can be demonstrated only in the presence of a functional retention (receptor) system for oestrogen. In contrast, no specific progesterone retention system has yet been demonstrated for hypothalamus or pituitary. Does progesterone interact with these target tissues in a novel manner? This seems unlikely since other steroids which have been studied—for example, adrenal corticoids¹⁷ and androgens¹⁸—have been found to bind to specific receptors in their target tissues. We therefore tested an alternate possibility that progesterone action on hypothalamus and pituitary might result in modification of the oestrogen receptor system. We tested ³H-oestradiol retention by hypothalamus and pituitary after in vivo treatment with progesterone (subcutaneous pellet; release rate=1.5–3 mg d⁻¹) of various durations from hours to days. In vitro ³H-oestradiol-specific retention by oestradiol–receptor complexes transferred to the nuclear fraction of these tissues was also compared for animals receiving previous in vivo progesterone treatment compared with ovariectomised animals not receiving progesterone treatment.