Supplemental Progesterone Delays Heat Termination and the Loss of Progestin Receptors from Hypothalamic Cell Nuclei in Female Guinea Pigs

Abstract

Previous studies indicate that the retention of hypothalamic nuclear progestin receptors parallels the expression of sexual receptivity in ovariectomized, hormonally treated guinea pigs. In this study, the effect of a supplementai progesterone injection on heat termination and retention of nuclear progestin receptors was examined. Ovariectomized guinea pigs were injected with 50 µg progesterone 48 h after receiving 4 µg estradiol benzoate and were tested hourly for lordosis. 8 h after progesterone treatment, animals received either 500 µg progesterone or the oil vehicle. The supplementai progesterone injection delayed the termination of heat by more than 2 h compared to oil-injected animals. The effect of supplemental progesterone on the retention of nuclear progestin receptors was then determined. Animals were killed 8, 10, or 14 h after the initial injection of progesterone, and cytosol and nuclear progestin receptor concentrations in mediobasai hypothalamus-preoptic area were determined. Supplemental progesterone further increased the level of nuclear progestin receptors measured at 10 h, and at 14 h these levels were still elevated above baseline. In contrast, nuclear progestin receptor levels in animals which received only the initial progesterone injection had returned to baseline by 14 h, a time when similarly treated animals were no longer receptive. These results suggest that the mechanism by which heat termination occurs may involve loss of nuclear progestin receptors.

Maintenance of Progesterone-Facilitated Sexual Behavior in Female Rats Requires Continued Hypothalamic Protein Synthesis and Nuclear Progestin Receptor Occupation*

“…In addition, administration of the progestin antagonist RU 486 to sexually receptive female guinea pigs results in both an abbreviation of the receptive period and a premature decrease in progesterone-occupied cell nuclear progestin receptor levels measured in the MBH (7). We have consistently found that as hypothalamic nuclear progestin receptor levels decrease, MAINTENANCE OF SEXUAL BEHAVIOR 299 fewer guinea pigs remain sexually responsive (7)(8)(9). At about the same time after progesterone treatment that nuclear progestin receptor levels decline to baseline levels, the period of sexual behavior terminates in similarly treated females.…”

“…We have recently provided evidence to support the hypothesis that in the female guinea pig, the period of sexual receptivity is maintained by an elevation in hypothalamic progesterone-occupied cell nuclear progestin receptors (6)(7)(8)(9). Treatment of OVX rats or guinea pigs with estradiol increases the number of progestin receptors in cytosol fractions obtained from several regions of the brain, including the mediobasal hypothalamuspreoptic area (MBH-POA) (10)(11)(12)(13).…”

“…This transient increase in nuclear progestin receptors is thought to alter the synthesis of specific proteins important for the activation of lordosis (19,20). Supplemental administration of estradiol or progesterone to hormonally treated sexually responsive guinea pigs delays both the termination of the receptive period and the loss of progestin receptors from MBH-POA cell nuclei (9,21). In addition, administration of the progestin antagonist RU 486 to sexually receptive female guinea pigs results in both an abbreviation of the receptive period and a premature decrease in progesterone-occupied cell nuclear progestin receptor levels measured in the MBH (7).…”