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      Neural and Hormonal Control of Sexual Behavior

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          Abstract

          Gonadal hormones contribute to the sexual differentiation of brain and behavior throughout the lifespan, from initial neural patterning to “activation” of adult circuits. Sexual behavior is an ideal system in which to investigate the mechanisms underlying hormonal activation of neural circuits. Sexual behavior is a hormonally regulated, innate social behavior found across species. Although both sexes seek out and engage in sexual behavior, the specific actions involved in mating are sexually dimorphic. Thus, the neural circuits mediating sexual motivation and behavior in males and females are overlapping yet distinct. Furthermore, sexual behavior is strongly dependent on circulating gonadal hormones in both sexes. There has been significant recent progress on elucidating how gonadal hormones modulate physiological properties within sexual behavior circuits with consequences for behavior. Therefore, in this mini-review we review the neural circuits of male and female sexual motivation and behavior, from initial sensory detection of pheromones to the extended amygdala and on to medial hypothalamic nuclei and reward systems. We also discuss how gonadal hormones impact the physiology and functioning of each node within these circuits. By better understanding the myriad of ways in which gonadal hormones impact sexual behavior circuits, we can gain a richer and more complete appreciation for the neural substrates of complex behavior.

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          Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males.

          Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown whether these dimorphisms control sex-typical behavior exclusively in one sex or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. Using a genetic strategy we developed, we have ablated one such dimorphic PR-expressing neuronal population located in the ventromedial hypothalamus (VMH). Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly defined, sexually dimorphic neuronal population in the brain. Moreover, we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Overshadowed by the amygdala: the bed nucleus of the stria terminalis emerges as key to psychiatric disorders

            The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases. Most research on stress and psychiatric diseases has focused on the amygdala, which regulates immediate responses to fear. However, the BNST, and not the amygdala, is the center of the psychogenic circuit from the hippocampus to the paraventricular nucleus. This circuit is important in the stimulation of the hypothalamic–pituitary–adrenal axis. Thus, the BNST has been largely overlooked with respect to its possible dysregulation in mood and anxiety disorders, social dysfunction and psychological trauma, all of which have clear gender disparities. In this review, we will look in-depth at the anatomy and projections of the BNST, and provide an overview of the current literature on the relevance of BNST dysregulation in psychiatric diseases.
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              Reframing sexual differentiation of the brain.

              In the twentieth century, the dominant model of sexual differentiation stated that genetic sex (XX versus XY) causes differentiation of the gonads, which then secrete gonadal hormones that act directly on tissues to induce sex differences in function. This serial model of sexual differentiation was simple, unifying and seductive. Recent evidence, however, indicates that the linear model is incorrect and that sex differences arise in response to diverse sex-specific signals originating from inherent differences in the genome and involve cellular mechanisms that are specific to individual tissues or brain regions. Moreover, sex-specific effects of the environment reciprocally affect biology, sometimes profoundly, and must therefore be integrated into a realistic model of sexual differentiation. A more appropriate model is a parallel-interactive model that encompasses the roles of multiple molecular signals and pathways that differentiate males and females, including synergistic and compensatory interactions among pathways and an important role for the environment.
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                Author and article information

                Journal
                Endocrinology
                Endocrinology
                endo
                Endocrinology
                Oxford University Press (US )
                0013-7227
                1945-7170
                October 2020
                26 August 2020
                26 August 2020
                : 161
                : 10
                : bqaa150
                Affiliations
                Department of Psychiatry and Behavioral Sciences, Stanford University , Stanford, California
                Author notes
                Correspondence: Kimberly J. Jennings, PhD, 1201 Welch Road, MSLS Building, Rm 154, Stanford University, Stanford, CA 94305. E-mail: kimjenn@ 123456stanford.edu .
                Author information
                http://orcid.org/0000-0003-0843-5052
                http://orcid.org/0000-0002-8921-5942
                Article
                bqaa150
                10.1210/endocr/bqaa150
                7507403
                32845294
                c404d859-8a0e-4301-b66b-b2a8c0c40461
                © Endocrine Society 2020.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 June 2020
                : 24 August 2020
                : 22 September 2020
                Page count
                Pages: 13
                Funding
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development, DOI 10.13039/100009633;
                Award ID: F32HD095597
                Categories
                Mini-Reviews
                AcademicSubjects/MED00250

                Endocrinology & Diabetes
                reproductive behavior,gonadal hormones,sex hormones,activation,sex differences

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