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

Abstract

The role of ongoing progesterone-directed protein synthesis and hypothalamic cell nuclear progestin receptor occupation in maintaining the duration of the period of sexual receptivity was determined in ovariectomized rats treated with 500 micrograms progesterone 44 h after receiving 2 micrograms estradiol benzoate. Injection of the protein synthesis inhibitor anisomycin (100 mg/kg BW) either 2 or 10 h after progesterone treatment resulted in decreased levels of both receptive and proceptive sexual behavior. Similarly, injection of RU 486, an antiprogestin, 2, 6, or 10 h after progesterone injection resulted in inhibition of sexual behavior within 4-8 h after administration. Using a modified cell nuclear isolation technique for the exchange assay of nuclear-bound progestin receptors, elevated levels of progestin binding in hypothalamic cell nuclear fractions were detected as late as 14 h after progesterone injection. By 18 h after progesterone injection, nuclear progestin receptor levels had returned to baseline, a time when the period of sexual behavior had terminated in similarly treated animals. These data suggest that continued progesterone action in hypothalamic cell nuclei is required for the maintenance of progesterone-facilitated sexual behavior in the female rat. Furthermore, they suggest that progesterone action maintains sexual responsiveness by altering the synthesis of a short-lived protein or set of proteins.

Strategies and Methods for Research on Sex Differences in Brain and Behavior

“…Ref. 26,27). Fadrozole is an effective inhibitor of aromatase, the enzyme catalyzing 17␤-estradiol synthesis from testosterone (e.g.…”

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

“…Classic intracellular PRs are highly expressed in the VMH of rodents and are upregulated by E 2 and/or P 4 coincident with lordosis [8][9][10]. Blocking actions at PRs in the VMH inhibits lordosis of naturally-receptive or ovx, hormone-primed rats [11][12][13][14][15][16]. Administration of PR ligands to ovx, E 2 -primed rats [15], but not PR knockout mice (PRKO), facilitates lordosis [17][18].…”

Dose-dependent effects of the antiprogestin, RU486, on sexual behavior of naturally cycling Fischer rats

“…Although classical intracellular progesterone receptors within the ventromedial nucleus have been clearly implicated in lordosis behavior [25, 67–69]; in other brain areas such as the medial preoptic area and ventral tegmental area, membrane progesterone receptors and/or neurotransmitter receptors such as GABA A may be sufficient to facilitate the behavior following progesterone treatment [18, 70, 71]. …”

“…Several lines of evidence allow the suggestion that intracellular progesterone receptors play an important role in progesterone’s ability to facilitate lordosis behavior [21–24]. For example, when ovariectomized rats are hormonally primed with progesterone following a dose of estradiol benzoate that is insufficient for induction of lordosis behavior: (a) compounds, such as RU486 (11β-(4-dimethylamino)phenyl-17β-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one), which can antagonize intracellular progesterone receptor-mediated events, block progesterone’s facilitation of lordosis behavior [20, 25, 26]; (b) hypothalamus infusion of antisense oligonucleotides to intracellular progesterone receptors blocks the facilitation [24, 27]; and (c) progesterone’s facilitation is reduced or absent in progesterone receptor knock out (PRKO) rodents [22, 28, 29]. However, when ovariectomized rats are treated with doses of estradiol benzoate that are sufficient to elicit lordosis behavior without progesterone priming, RU486 does not reduce lordosis behavior and has led to suggestions that intracellular progesterone receptors may not be required for estrogen-induced lordosis behavior [20, 26, 30–32].…”