Sex differences in the neural circuit that mediates female sexual receptivity

Flanagan‐Cato, Loretta M.

doi:10.1016/j.yfrne.2011.02.008

Cited by 80 publications

(62 citation statements)

References 183 publications

(235 reference statements)

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“…The VMHvl has a pivotal role in female sexual behavior (12,35), and the ARC is thought to be essential in the negative feedback actions of estrogen (31,44,45). Importantly, ARC neurons are prime sensors of the internal environment integrating metabolic and reproductive functions (9,23).…”

Section: Discussionmentioning

confidence: 99%

Estradiol modulates Kiss1 neuronal response to ghrelin

Frazão

Lemko

Silva

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Ghrelin is a metabolic signal regulating energy homeostasis. Circulating ghrelin levels rise during starvation and fall after a meal, and therefore, ghrelin may function as a signal of negative energy balance. Ghrelin may also act as a modulator of reproductive physiology, as acute ghrelin administration suppresses gonadotropin secretion and inhibits the neuroendocrine reproductive axis. Interestingly, ghrelin's effect in female metabolism varies according to the estrogen milieu predicting an interaction between ghrelin and estrogens, likely at the hypothalamic level. Here, we show that ghrelin receptor (GHSR) and estrogen receptor-␣ (ER␣) are coexpressed in several hypothalamic sites. Higher levels of circulating estradiol increased the expression of GHSR mRNA and the co-xpression of GHSR mRNA and ER␣ selectively in the arcuate nucleus (ARC). Subsets of preoptic and ARC Kiss1 neurons coexpressed GHSR. Increased colocalization was observed in ARC Kiss1 neurons of ovariectomized estradiol-treated (OVX ϩ E2; 80%) compared with ovariectomized oil-treated (OVX; 25%) mice. Acute actions of ghrelin on ARC Kiss1 neurons were also modulated by estradiol; 75 and 22% of Kiss1 neurons of OVX ϩ E2 and OVX mice, respectively, depolarized in response to ghrelin. Our findings indicate that ghrelin and estradiol may interact in several hypothalamic sites. In the ARC, high levels of E2 increase GHSR mRNA expression, modifying the colocalization rate with ER␣ and Kiss1 and the proportion of Kiss1 neurons acutely responding to ghrelin. Our findings indicate that E2 alters the responsiveness of kisspeptin neurons to metabolic signals, potentially acting as a critical player in the metabolic control of the reproductive physiology. kisspeptin; hypothalamus; metabolism; growth hormone secretagogue receptor; reproduction IN MAMMALS, THE ABILITY TO REPRODUCE is gated by the availability of energy stores (25,49). Reproduction is metabolically expensive, and during starvation fertility is stopped to conserve energy for basic survival. Accumulating evidence has implicated circulating hormones as a means of transmitting information regarding peripheral energy availability to the central circuitry that controls the reproductive system. Among these metabolic signals is the stomach-derived hormone ghrelin (23,46). Ghrelin was recognized originally for its growth hormonestimulating action, but extensive research has since demonstrated that ghrelin is also a direct regulator of metabolism and energy balance (22,28,55). Ghrelin promotes the storage of lipids as fat, induces glucagon release, and suppresses insulin secretion and sensitivity (4, 5, 47). Interestingly, the effects of ghrelin to increase body weight vary according to the estrogen milieu, as a more pronounced orexigenic effect is observed in females upon ovariectomy (3, 6). In cycling rats, ghrelin stimulation of food intake is observed only in females in diestrus (when estrogen levels are low). Moreover, males treated with estradiol are resistant to the stimulatory effects of ghrelin...

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Section: Discussionmentioning

confidence: 99%

Estradiol modulates Kiss1 neuronal response to ghrelin

Frazão

Lemko

Silva

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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“…The organization of brain sex differences during this critical period is important for adult reproductive function [1,2]. Studies have shown that administration of estradiol-17β or compounds with estrogenic activity to newborn rats during critical period results in irreversible masculinization as well as defeminization in the brain resulting in abnormal sexual behavior as adults [1,[3][4][5][6]. Recently we observed that neonatal exposure to estradiol-17β in the female rat resulted in up-regulation of COX-2 and increased size of SDN-POA compared to control during adulthood [7].…”

Section: Introductionmentioning

confidence: 99%

Neonatal exposure to estradiol-17β modulates tumour necrosis factor alpha and cyclooxygenase-2 expression in brain and also in ovaries of adult female rats

Shridharan

Krishnagiri

Govindaraj

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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Abstract:The sexually dimorphic organization in perinatal rat brain is influenced by steroid hormones. Exposure to high levels of estrogen or endocrine-disrupting compounds during perinatal period may perturb this process, resulting in compromised reproductive physiology and behavior as observed in adult In our recent observation neonatal exposure of the female rats to estradiol-17β resulted in down-regulation of TNF-α, up-regulation of COX-2 and increase in SDN-POA size in pre-optic area in the adulthood. It is known that the control of reproductive performance in female involves a complex interplay of the hypothalamus, pituitary, and ovary. The present study was undertaken to understand the possible molecular mechanism involved in changes observed in the ovarian morphology and expression of selected genes in the ovary. Administration of estradiol-17β (100 μg) on day 2 and 3 after birth revealed up-regulation of ER-α, ER-β, COX-2 and down-regulation of TNF-α expression. Also the decrease in the ovarian weight, altered ovarian morphology and changes in the 2D protein profiles were also seen. This is apparently the first report documenting that neonatal estradiol exposure modulates TNF-α and COX-2 expression in the ovary as seen during adult stage. Our results permit us to suggest that cues originating from the modified brain structure due to neonatal exposure of estradiol-17β remodel the ovary at the molecular level in such a way that there is a disharmony in the reproductive function during adulthood and these changes are perennial and can lead to infertility and changes of reproductive behavior.

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“…Higher brain areas are required to mediate the hormonal control of the reflex. In particular, the ventromedial nucleus (VMN) of the hypothalamus is critical for this hormonal control and communicates with the dorsal and lateral portions of the periacqueductal gray (PAG) of the midbrain (Flanagan-Cato, 2011; Kow and Pfaff, 1998). This VMN-PAG information is thought to be critical to estrogen’s ability to facilitate the reflex and to coordinate the behavior with the female’s ability to procreate.…”

Section: 0 Introduction and Overviewmentioning

confidence: 99%

Pharmacology of serotonin and female sexual behavior

Uphouse

2014

Pharmacology Biochemistry and Behavior

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In this review, first a historical perspective of serotonin’s (5-HT) involvement in female sexual behavior is presented. Then an overview of studies implicating 5-HT is presented. The effect of drugs that increase or decrease CNS levels of 5-HT is reviewed. Evidence is presented that drugs which increase 5-HT have negative effects on female sexual behavior while a decrease in 5-HT is associated with facilitation of sexual behavior. Studies with compounds that act on 5-HT1, 5-HT2 or 5-HT3 receptors are discussed. Most evidence indicates that 5-HT1A receptor agonists inhibit sexual behavior while 5-HT2 or 5-HT3 receptors may exert a positive influence. There is substantial evidence to support a role for 5-HT in the modulation of female consummatory sexual behavior, but studies on the role of 5-HT in other elements of female sexual behavior (e.g. desire, motivation, sexual appetite) are few. Future studies should be directed at determining if these additional components of female sexual behavior are also modulated by 5-HT.

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Sex differences in the neural circuit that mediates female sexual receptivity

Cited by 80 publications

References 183 publications

Estradiol modulates Kiss1 neuronal response to ghrelin

Estradiol modulates Kiss1 neuronal response to ghrelin

Neonatal exposure to estradiol-17β modulates tumour necrosis factor alpha and cyclooxygenase-2 expression in brain and also in ovaries of adult female rats

Pharmacology of serotonin and female sexual behavior

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