Progestins affect reproductive behavior and androgen receptor dynamics in male guinea pig brain

Connolly, Peter B.; Resko, John A.

doi:10.1016/0006-8993(89)91681-8

Cited by 22 publications

(6 citation statements)

References 24 publications

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“…Various studies investigating the effects of progesterone on reproductive behavior used supraphysiological levels of progesterone that would greatly exceed its levels accounted for by ovarian secretion (Erpino 1975, Connolly & Resko 1989). However, the endogenous levels of progesterone can be locally regulated in specific tissues or regions of the brain (Le Goascogne et al .…”

Section: Discussionmentioning

confidence: 99%

Aromatase promoter I.f is regulated by progesterone receptor in mouse hypothalamic neuronal cell lines

Yılmaz¹,

Wolfe²,

Zhao³

et al. 2011

Journal of Molecular Endocrinology

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Aromatase catalyzes the conversion of C19 steroids to estrogens. Aromatase and progesterone, both of which function at different steps of steroidogenesis, are crucial for the sexually dimorphic development of the fetal brain and the regulation of gonadotropin secretion and sexual interest in adults. The aromatase gene (Cyp19a1) is selectively expressed in distinct neurons of the mouse hypothalamus through a distal brain-specific promoter, I.f, located ~40 kb upstream of the coding region. However, the regulation of aromatase expression in the brain is not well understood. In this study, we investigated a short feedback effect of progesterone analogues on aromatase mRNA expression and enzyme activity in estrogen receptor α (Esr1)-positive or -negative mouse embryonic hypothalamic neuronal cell lines that express aromatase via promoter I.f. In a hypothalamic neuronal cell line that highly expresses aromatase, progesterone receptor (Pgr), and Esr1, a progesterone agonist, R5020, inhibited aromatase mRNA level and enzyme activity. The inhibitory effect of R5020 was reversed by its antagonist, RU486. Deletion mutants of promoter I.f suggested that inhibition of aromatase expression by progesterone is conferred by the nt −1000/ −500 region, and R5020 enhanced binding of Pgr to the nt −800/ −600 region of promoter I.f. Small interfering RNA knockdown of Pgr eliminated progesterone-dependent inhibition of aromatase mRNA and enzyme activity. Taken together, progesterone enhances recruitment of Pgr to specific regions of the promoter I.f of Cyp19a1 and regulates aromatase expression in hypothalamic neurons.

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Section: Discussionmentioning

confidence: 99%

Aromatase promoter I.f is regulated by progesterone receptor in mouse hypothalamic neuronal cell lines

Yılmaz¹,

Wolfe²,

Zhao³

et al. 2011

Journal of Molecular Endocrinology

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“…[Unimplanted intact males differing in courtship intensity representing these two populations also do not have differential baseline abundances of androgen receptor-or progesterone receptor-mRNA in these nuclei (D. Crews, J. Godwin, and M. Grammer, unpublished data)]. Progesterone is known to downregulate nuclear AR protein, but not cytosolic AR, in the AH-POA and pituitary of male guinea pigs administered either progesterone or the synthetic progestin agonist R5020 (Connolly and Resko, 1989). A progesteronemediated regulation of AR-mRNA could be important in the medial POA, because AR-and PR-mRNA are codistributed in this area.…”

Section: Discussionmentioning

confidence: 99%

Intrahypothalamic Implantation of Progesterone in Castrated Male Whiptail Lizards (Cnemidophorus inornatus) Elicits Courtship and Copulatory Behavior and Affects Androgen Receptor- and Progesterone Receptor-mRNA Expression in the Brain

et al. 1996

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A primary tenet of behavioral neuroendocrinology is that gonadal steroid hormones act on limbic nuclei to activate mating behavior in vertebrates. Traditionally, research has focused on the regulation of male-typical sexual behavior by testicular androgens and female-typical sexual behavior by ovarian estrogen and progesterone. Indeed, progesterone generally is regarded as an antiandrogen, acting centrally to inhibit sexual behavior in males. However, experiments with lizards, and more recently with rats, have challenged this paradigm. For example, exogenous progesterone induces mating behavior in some, but not all, castrated male whiptail lizards. The present study determined that implantation of progesterone into the anterior hypothalamus preoptic area of castrated, progesterone-sensitive males completely restored sexual behavior but failed to elicit sexual activity in castrated, progesterone-insensitive males. Further, androgen receptor -and progesterone receptor-mRNA expression in specific brain regions was significantly different in progesterone-sensitive versus progesterone-insensitive animals. Progesterone-sensitive males showed significantly higher relative abundance of androgen receptor-mRNA in the preoptic area, amygdala, and lateral septum, as compared with progesterone-insensitive animals receiving the same treatment. In contrast, progesterone receptor-mRNA abundance was lower in preoptic area of progesterone-sensitive males than in progesterone-insensitive males. No differences were found in the baseline abundance of androgen receptor-or progesterone receptor-mRNA in these nuclei between control groups of progesterone-sensitive and progesterone-insensitive males who were castrated but not implanted. This suggests that progesterone differentially regulates its own receptor as well as androgen receptor in areas of the brain involved in the control of sexual behavior of males and that the nature of this regulation shows individual variability.

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“…Progesterone could act indirectly via interactions of progesterone metabolites with g-aminobutyric acid type A (GABA A ) receptors (Rupprecht & Holsboer 1999;Miczek et al 2003) or more directly by binding to the progesterone receptor or even to the androgen receptor (Bullock et al 1978;Crews et al 1996). Progesterone has been demonstrated to affect the expression of androgen receptor mRNA in male guinea-pigs (Cavia porcellus; Connolly & Resko 1989) and whiptail lizards (Cnemidophorus inornatus: Crews et al 1996). Further, progesterone attenuates testosterone-induced behaviours in male birds (Erickson et al 1967;Bottoni et al 1985) and female mammals (Barfield 1984;Albert et al 1992), and it protects female guinea-pigs from the masculinizing actions of testosterone ( Diamond & Young 1963).…”

Section: Discussionmentioning

confidence: 99%

Progesterone modulates aggression in sex-role reversed female African black coucals

et al. 2008

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Testosterone is assumed to be the key hormone related to resource-defence aggression. While this role has been confirmed mostly in the context of reproduction in male vertebrates, the effect of testosterone on the expression of resource-defence aggression in female vertebrates is not so well established. Furthermore, laboratory work suggests that progesterone inhibits aggressive behaviour in females. In this study, we investigated the hormonal changes underlying territorial aggression in free-living female African black coucals, Centropus grillii (Aves; Cuculidae). Females of this sex-role reversed polyandrous bird species should be particularly prone to be affected by testosterone because they aggressively defend territories similar to males of other species. We show, however, that territorial aggression in female black coucals is modulated by progesterone. After aggressive territorial challenges female black coucals expressed lower levels of progesterone than unchallenged territorial females and females without territories, suggesting that progesterone may suppress territorial aggression and is downregulated during aggressive encounters. Indeed, females treated with physiological concentrations of progesterone were less aggressive than females with placebo implants. This is one of the first demonstrations of a corresponding hormone-behaviour interaction under challenged and experimental conditions in free-living females. We anticipate that our observation in a sex-role reversed species may provide a more general mechanism, by which progesterone-in interaction with testosterone-may regulate resource-defence aggression in female vertebrates.

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Progestins affect reproductive behavior and androgen receptor dynamics in male guinea pig brain

Cited by 22 publications

References 24 publications

Aromatase promoter I.f is regulated by progesterone receptor in mouse hypothalamic neuronal cell lines

Aromatase promoter I.f is regulated by progesterone receptor in mouse hypothalamic neuronal cell lines

Intrahypothalamic Implantation of Progesterone in Castrated Male Whiptail Lizards (Cnemidophorus inornatus) Elicits Courtship and Copulatory Behavior and Affects Androgen Receptor- and Progesterone Receptor-mRNA Expression in the Brain

Progesterone modulates aggression in sex-role reversed female African black coucals

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