Prenatal Inhibition of Aromatase Activity Affects Luteinizing Hormone Feedback Mechanisms and Reproductive Behaviors of Adult Guinea Pigs1

Choate, Jerome V.A.; Resko, John A.

doi:10.1095/biolreprod51.6.1273

Cited by 20 publications

(5 citation statements)

References 27 publications

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“…Female guinea pigs ( Cavia porcellus ) subjected to prenatal ATD exposure had decreased mounting activity but comparable responses were not observed in males subjected to similar AI exposure ( Roy, 1992 ). However, another study testing the effects of developmental exposure to ATD in guinea pigs (gestational day 30 to day 55) reported that both males and females were irresponsive to the negative feedback effects of E2 benzoate or LH secretion, and ATD-treated males demonstrated increased lordosis behavior compared to control males ( Choate and Resko, 1994 ). However, no changes in mounting or lordosis behavior were evident in ATD-treated female guinea pigs ( Choate and Resko, 1994 ).…”

Section: Aromatase and Sociosexual Behaviorsmentioning

confidence: 99%

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Shay

Vieira‐Potter

Rosenfeld

2018

Front. Mol. Neurosci.

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Aromatase is the enzyme responsible for converting testosterone to estradiol. In mammals, aromatase is expressed in the testes, ovaries, brain, and other tissues. While estrogen is traditionally associated with reproduction and sexual behavior in females, our current understanding broadens this perspective to include such biological functions as metabolism and cognition. It is now well-recognized that aromatase plays a vital lifetime role in brain development and neurobehavioral function in both sexes. Thus, ongoing investigations seek to highlight potentially vital sex differences in the role of aromatase, particularly regarding its centrally mediated effects. To characterize the role of aromatase in mediating such functions, effects of aromatase inhibitor (AI) treatments on humans and animal models have been determined. Aromatase knockout (ArKO) mice that systemically lack the enzyme have also been employed. Humans possessing mutations in the gene encoding aromatase, CYP19, have also provided critical insight into how aromatase affects brain function in a possible sex-dependent manner. A better understanding of how AIs, used to treat breast cancer and other clinical conditions, may detrimentally affect neurobehavioral responses will likely promote development of future therapies to combat these effects. Herein, we will provide a critical review of the current knowledge of sex differences in aromatase regulation of various neurobehavioral functions. Although many species have been used to better understand the functions of aromatase, this review focuses on rodent models and humans. Critical gaps in our present understanding of this area will be considered, and important future research directions will be discussed.

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Section: Aromatase and Sociosexual Behaviorsmentioning

confidence: 99%

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Shay

Vieira‐Potter

Rosenfeld

2018

Front. Mol. Neurosci.

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“…In males, testosterone is secreted from the developing testis and is subsequently aromatised in the brain and other tissues to oestradiol by the enzyme aromatase. Prenatal treatment with the aromatase inhibitor, 1,4,6‐androstatrien‐3,17‐dione disrupts LH responses to oestradiol in adult male guinea pigs (11), and affects male‐typical sex behaviour in guinea pigs (12), sheep (13) and rats (14–16), indicating that the prenatal aromatisation of testosterone to oestradiol is crucial to the normal development of reproductive behaviours and responses to gonadal hormones in adulthood. Accordingly, perinatal treatment with exogenous oestradiol defeminises the GnRH/LH system in female rats (9, 17, 18).…”

mentioning

confidence: 99%

Aromatase Knockout Mice Show Normal Steroid‐Induced Activation of Gonadotrophin‐Releasing Hormone Neurones and Luteinising Hormone Surges With a Reduced Population of Kisspeptin Neurones in the Rostral Hypothalamus

Szymanski

Bakker

2012

J Neuroendocrinology

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The capacity to generate a preovulatory surge of gonadotrophinreleasing hormone (GnRH) ⁄ luteinising hormone (LH) in response to gonadal steroids is perhaps the most robust sexually differentiated endocrine response in rodents, with only females being capable of generating regular LH surges. The release of LH from the pituitary is stimulated by the secretion of GnRH from a diffuse population of neurones in the hypothalamus, which is in turn modulated by the actions of circulating oestradiol and progesterone. During most of the oestrous cycle, oestrogens exert a negative-feedback on the hypothalamic-pituitary axis. By contrast, on the afternoon of pro-oestrous, oestrogens and ⁄ or progesterone exert a positive-feedback on the hypothalamic-pituitary axis, leading to a massive release of GnRH and, subsequently, LH, and in turn to ovulation, at the same time as facilitating sexual behaviour (1-3). Thus, ovarian oestradiol secreted from metoestrous through early pro-oestrous by the developing follicle stimulates the release of GnRH and sensitises the pituitary gland to become more responsive to hypothalamic GnRH (4). The hypothalamic-pituitary axis in males, on the other hand, does not show positive-feedback in response to oestradiol and males are not able to support ovulation when implanted with ovarian tissue as adults (5). Journal of NeuroendocrinologyCorrespondence to: Julie Bakker, GIGA Neurosciences, University of Liège B36, Avenue de l'Hopital, 4000 Liège, Belgium (e-mail: jbakker@ulg.ac.be).We recently reported that female aromatase knockout (ArKO) mice show deficits in sexual behaviour and a decreased population of kisspeptin-immunoreactive neurones in the rostral periventricular area of the third ventricle (RP3V), resurrecting the question of whether oestradiol actively contributes to female-typical sexual differentiation. To further address this question, we assessed the capacity of ArKO mice to generate a steroid-induced luteinising hormone (LH) surge. Adult, gonadectomised wild-type (WT) and ArKO mice were given silastic oestradiol implants s.c. and, 1 week later, received s.c. injections of either oestradiol benzoate (EB) followed by progesterone, EB alone, or no additional steroids to activate gonadotrophin-releasing hormone (GnRH) neurones and generate an LH surge. Treatment with EB and progesterone induced significant Fos ⁄ GnRH double-labelling and, consequently, an LH surge in female WT and in ArKO mice of both sexes but not in male WT mice. ArKO mice of both sexes had fewer cells expressing Kiss-1 mRNA in the RP3V compared to female WT mice but had more Kiss-1 mRNA-expressing cells compared to WT males, reflecting an incomplete sexual differentiation of this system. To determine the number of cells expressing kisspeptin, the same experimental design was repeated in Experiment 2 with the addition of groups of WT and ArKO mice that were given EB + progesterone and sacrificed 2 h before the expected LH surge. No differences were observed in the number of kisspeptin-immunoreactive cells 2 h before and...

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“…By contrast, ARs appear to primarily mediate defeminisation of the LH surge mechanism in male guinea pigs , whereas, in male monkeys, goats and men, the LH surge mechanism is functional . Most experiments in rats, mice and guinea pigs support the conclusion that defeminisation of sexual receptivity depends on aromatisation . By contrast, prenatal treatment with either testosterone or DHT defeminises female sexual behaviour in monkeys .…”

Section: Discussionmentioning

confidence: 97%

Effects of Long‐Term Flutamide Treatment During Development on Sexual Behaviour and Hormone Responsiveness in Rams

Roselli

Meaker

Stormshak

et al. 2016

J Neuroendocrinology

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Testosterone (T) exposure during midgestation differentiates neural circuits controlling sex-specific behaviors and patterns of gonadotropin secretion in male sheep. T acts through androgen receptors (AR) and/or after aromatization to estradiol and binding to estrogen receptors. The current study assessed the role of AR activation in male sexual differentiation. We compared rams that were exposed to the AR antagonist flutamide (Flu) throughout the critical period (i.e. day 30 – 90 of gestation) to control rams and ewes that received no prenatal treatments. The external genitalia of all Flu rams were phenotypically female. Testes were positioned subcutaneously in the inguinal region of the abdomen, exhibited seasonally impaired androgen secretion and were azospermic. Flu rams displayed male-typical precopulatory and mounting behaviors, but could not intromit or ejaculate because they lacked a penis. Flu rams exhibited greater mounting behavior than control rams, and like controls, showed sexual partner preferences for estrous ewes. Neither control nor Flu rams responded to estradiol treatments with displays of female-typical receptive behavior or LH surge responses; whereas all control ewes responded as expected. The ovine sexually dimorphic nucleus in Flu rams was intermediate in volume between control rams and ewes and significantly different from both. . These results indicate that prenatal antiandrogen exposure is not able to block male sexual differentiation in sheep and suggest that compensatory mechanisms intervene to maintain sufficient androgen stimulation during development.

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Prenatal Inhibition of Aromatase Activity Affects Luteinizing Hormone Feedback Mechanisms and Reproductive Behaviors of Adult Guinea Pigs1

Cited by 20 publications

References 27 publications

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses

Aromatase Knockout Mice Show Normal Steroid‐Induced Activation of Gonadotrophin‐Releasing Hormone Neurones and Luteinising Hormone Surges With a Reduced Population of Kisspeptin Neurones in the Rostral Hypothalamus

Effects of Long‐Term Flutamide Treatment During Development on Sexual Behaviour and Hormone Responsiveness in Rams

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