scholarly journals Brain Aromatase and the Regulation of Sexual Activity in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (10) ◽  
Author(s):  
David C Brooks ◽  
John S Coon V ◽  
Cihangir M Ercan ◽  
Xia Xu ◽  
Hongxin Dong ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Sexual Activity ◽  
Adult Brain ◽  
Whole Body ◽  
Male Mice ◽  
Negative Feedback Regulation ◽  
Male Sexual Behavior ◽  
Brain Physiology ◽  
Brain Aromatase ◽  
The Brain

Abstract The biologically active estrogen estradiol has important roles in adult brain physiology and sexual behavior. A single gene, Cyp19a1, encodes aromatase, the enzyme that catalyzes the conversion of testosterone to estradiol in the testis and brain of male mice. Estradiol formation was shown to regulate sexual activity in various species, but the relative contributions to sexual behavior of estrogen that arises in the brain versus from the gonads remained unclear. To determine the role of brain aromatase in regulating male sexual activity, we generated a brain-specific aromatase knockout (bArKO) mouse. A newly generated whole-body total aromatase knockout mouse of the same genetic background served as a positive control. Here we demonstrate that local aromatase expression and estrogen production in the brain is partially required for male sexual behavior and sex hormone homeostasis. Male bArKO mice exhibited decreased sexual activity in the presence of strikingly elevated circulating testosterone. In castrated adult bArKO mice, administration of testosterone only partially restored sexual behavior; full sexual behavior, however, was achieved only when both estradiol and testosterone were administered together. Thus, aromatase in the brain is, in part, necessary for testosterone-dependent male sexual activity. We also found that brain aromatase is required for negative feedback regulation of circulating testosterone of testicular origin. Our findings suggest testosterone activates male sexual behavior in part via conversion to estradiol in the brain. These studies provide foundational evidence that sexual behavior may be modified through inhibition or enhancement of brain aromatase enzyme activity and/or utilization of selective estrogen receptor modulators.

scholarly journals OR09-03 Brain Aromatase Is Essential for Regulation of Sexual Activity in Male Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
David C Brooks ◽  
Hong Zhao ◽  
John Coon V ◽  
C Mutlu Ercan ◽  
Hongxin Dong ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Mouse Model ◽  
Sexual Activity ◽  
Sex Hormone ◽  
Splice Acceptor Site ◽  
Male Mice ◽  
Male Sexual Behavior ◽  
Estrogen Production ◽  
Brain Aromatase ◽  
The Brain

Abstract Introduction: The biologically active form of estrogen, estradiol (E2), has important organizational roles in brain development and activational roles in adult brain physiology and behavior. It has been proposed that E2 formation in the brain might regulate sexual activity in various species. The mechanisms that link estrogen formation in the brain and sexual behavior, however, remain unclear. Aromatase is the key enzyme that catalyzes the conversion of testosterone (T) to E2 in the testis and brain of male mice. To determine the role of brain aromatase in male sexual activity, we generated a brain-specific aromatase knockout (bArKO) mouse model. Additionally, a newly generated total aromatase knockout (tArKO) mouse model served as a positive control. Methods: We generated the floxed aromatase mice (Aromfl/fl), which flanked the transcription and translation start sites and the common splice acceptor site for the upstream brain promoter I.f of the aromatase gene. We then crossed Nestin-Cre mice with Aromfl/fl mice to generate bArKO mice. Using the same Aromfl/fl mice, we bred tArKO via crossing with ZP3-Cre mice. Circulating and tissue (brain and testis) E2 levels were measured using liquid chromatography-tandem mass spectrometry. We assessed sexual activity in 12-14 week-old bArKO, tArKO and littermate control males over two 30-minute trials. The interactions were monitored and videotaped, and the videotape was scored for the sexual activity. To investigate whether the lack of estrogen production in the brain was causative for altered sexual behavior, 20 bArKO and 20 control mice were castrated at ~nine weeks of age and supplemented with exogenous sex hormone via 60-day time release pellet implantation. Results: E2 levels are significantly decreased in the brain but not the testis of bArKO mice as compared to control mice (P < 0.05, n=6-12). As expected, E2 levels in the brain and testis are significantly lower in tArKO mice compared with their WT littermates (n=6-9). Furthermore, we demonstrate that local aromatase expression and estrogen production in the brain is required for male sexual behavior and sex hormone homeostasis. Male bArKO mice exhibited significantly decreased sexual activity in the presence of strikingly elevated circulating T (n=5). In castrated adult bArKO mice, administration of E2 together with T restored maximum sexual behavior (n=5). Thus, aromatase in the brain is necessary for T-dependent male sexual activity. We also found that brain aromatase is required for negative feedback regulation of circulating T of testicular origin. Conclusion: Our findings suggest T activates male sexual behavior in part via conversion to E2 in the brain and provide the foundation for inhibition or enhancement of brain aromatase enzyme activity and/or utilization of selective estrogen receptor modulators in modifying sexual behavior. DCB and HZ contributed equally to this work.

Gene expression profiling in the neuroendocrine brain of male goldfish (Carassius auratus) exposed to 17α-ethinylestradiol

2006 ◽  
Vol 27 (3) ◽  
pp. 328-336 ◽  
Author(s):  
Christopher J. Martyniuk ◽  
Huiling Xiong ◽  
Kate Crump ◽  
Suzanne Chiu ◽  
Ravinder Sardana ◽  
...  
Keyword(s):  
Large Scale ◽  
Cell Metabolism ◽  
Endocrine Disrupting Chemicals ◽  
Cdna Array ◽  
Adult Brain ◽  
Intact Male ◽  
Mature Adult ◽  
Goldfish Carassius Auratus ◽  
Brain Aromatase ◽  
The Brain

17-α Ethinylestradiol (EE2), a pharmaceutical estrogen, is detectable in water systems worldwide. Although studies report on the effects of xenoestrogens in tissues such as liver and gonad, few studies to date have investigated the effects of EE2 in the vertebrate brain at a large scale. The purpose of this study was to develop a goldfish brain-enriched cDNA array and use this in conjunction with a mixed tissue carp microarray to study the genomic response to EE2 in the brain. Gonad-intact male goldfish were exposed to nominal concentrations of 0.1 nM (29.6 ng/l) and 1.0 nM (296 ng/l) EE2 for 15 days. Male goldfish treated with the higher dose of EE2 had significantly smaller gonads compared with controls. Males also had a significantly reduced level of circulating testosterone (T) and 17β-estradiol (E2) in both treatment groups. Candidate genes identified by microarray analysis fall into functional categories that include neuropeptides, cell metabolism, and transcription/translation factors. Differentially expressed genes verified by real-time RT-PCR included brain aromatase, secretogranin-III, and interferon-related developmental regulator 1. Our results suggest that the expression of genes in the sexually mature adult brain appears to be resistant to low EE2 exposure but is affected significantly at higher doses of EE2. This study demonstrates that microarray technology is a useful tool to study the effects of endocrine disrupting chemicals on neuroendocrine function and suggest that exposure to EE2 may have significant effects on localized E2 synthesis in the brain by affecting transcription of brain aromatase.

Steroid-independent male sexual behavior in B6D2F2 male mice

2016 ◽  
Vol 85 ◽  
pp. 26-29
Author(s):  
Christine M. McInnis ◽  
Samitha Venu ◽  
Jin Ho Park
Keyword(s):  
Sexual Behavior ◽  
Male Mice ◽  
Male Sexual Behavior

Effects of a novel partner and sexual satiety on the expression of male sexual behavior and brain aromatase activity in quail

2019 ◽  
Vol 359 ◽  
pp. 502-515
Author(s):  
Catherine de Bournonville ◽  
Mélanie Schmit ◽  
Maxim Telle ◽  
Lucas Court ◽  
Gregory F. Ball ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Aromatase Activity ◽  
Male Sexual Behavior ◽  
Brain Aromatase

scholarly journals Combined Effects of Oligopeptides Isolated from Panax ginseng C.A. Meyer and Ostrea gigas Thunberg on Sexual Function in Male Mice

2021 ◽  
Vol 18 (5) ◽  
pp. 2349
Author(s):  
Di Li ◽  
Jinwei Ren ◽  
Lixia He ◽  
Jingqin Sun ◽  
Peng Liu ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Sexual Function ◽  
Whey Protein ◽  
Corpus Cavernosum ◽  
Vehicle Control ◽  
Control Group ◽  
Male Mice ◽  
Vehicle Control Group ◽  
Male Sexual Behavior ◽  
Male Sexual Function

Male sexual debility affects patients’ confidence and damages the relationship between the couples and thus affects the stability of the family. This study aimed to investigate the effects of oligopeptides isolated from ginseng and oyster (GOPs and OOPs), separately and in combination, on sexual function in male mice. In the first experiment, male mice were randomly divided into five groups: vehicle control group; whey protein (125.0 mg kg−1) group; and GOPs 62.5, 125.0, and 250.0 mg kg−1 groups. In the second experiment, male mice were randomly divided into five groups: vehicle control group, whey protein (160.0 mg kg−1) group, and OOPs 80.0, 160.0, and 320.0 mg kg−1 groups. In the third experiment, male mice were randomly divided into six groups: vehicle control group, whey protein (222.5 mg kg−1) group, and GOPs + OOPs 62.5 + 160.0, 62.5 + 320.0, and 125.0 + 160.0, 125.0 + 320.0 mg kg−1 groups. Test substances were given by gavage once a day for 30 days. The sexual behavior parameters, serum nitric oxide (NO), testosterone, cyclic guanosine monophosphate (cGMP), and phosphodiesterase-5 (PDE5) concentrations were detected. We found that GOPs at 250.0 mg kg−1 improved male sexual behavior, NO, and testosterone content, whereas GOPs at 62.5 and 125.0 mg kg−1 and OOPs at 80.0, 160, and 320 mg kg−1 did not have significant effects. The combination of 62.5 mg kg−1 GOPs + 160.0 mg kg−1 OOPs and the combination of 125.0 mg kg−1 GOPs + 320.0 mg kg−1 OOPs improved male sexual behavior, serum NO, testosterone, and cGMP contents and decreased PDE5 content. The combination of 62.5 mg kg−1 GOPs and 160.0 mg kg−1 OOPs had the best effects among four combined groups. These results suggested that GOPs in combination with OOPs had the synergistic effects of enhancing male sexual function, probably via elevating serum testosterone, NO, and corpus cavernosum cGMP level and decreasing the corpus cavernosum PDE5 level. GOPs and OOPs could be novel natural agents for improving male sexual function.

Sexual Behavior in Males From a Neuroendocrine Perspective

2018 ◽  
Author(s):  
Jacques Balthazart ◽  
Gregory F. Ball
Keyword(s):  
Sexual Behavior ◽  
Critical Role ◽  
Time Frame ◽  
Behavioral Activity ◽  
Inactive Compound ◽  
Male Sexual Behavior ◽  
Brain Aromatase ◽  
Rapid Changes ◽  
Androgenic Steroids ◽  
Time Frames

It is well established that testosterone from testicular origin plays a critical role in the activation of male sexual behavior in most, if not all, vertebrate species. These effects take place to a large extent in the preoptic area although other brain sites are obviously also implicated. In its target areas, testosterone is actively metabolized either into estrogenic and androgenic steroids that have specific behavioral effects or into inactive metabolites. These transformations either amplify the behavioral activity of testosterone or, alternatively, metabolism to an inactive compound dissipates any biological effect. Androgens and estrogens then bind to nuclear receptors that modulate the transcription of specific genes. This process is controlled by a variety of co-activators and co-repressors that, respectively, enhance or inhibit these transcriptional processes. In addition, recent work has shown that the production of estrogens by brain aromatase can be modulated within minutes by changes in neural activity and that these rapid changes in neuroestrogen production impact sexual behavior, in particular sexual motivation within the same time frame. Estrogens thus affect specific aspects of male sexual behavior in two different time frames via two types of mechanisms that are completely different. Multiple questions remain open concerning the cellular brain mechanisms that mediate testosterone action on male sexual behavior.

Peripubertal gonadal steroids are necessary for steroid-independent male sexual behavior in castrated B6D2F1 male mice

2019 ◽  
Vol 113 ◽  
pp. 38-46 ◽  
Author(s):  
Jay Scott Templin ◽  
Joshua C. Wyrosdic ◽  
Caroline D. David ◽  
Brianna N. Wyrosdic ◽  
Hannah E. Lapp ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Gonadal Steroids ◽  
Male Mice ◽  
Male Sexual Behavior

X-irradiation lethality aggravated by sexual activity of male mice

1960 ◽  
Vol 198 (6) ◽  
pp. 1352-1354 ◽  
Author(s):  
Roberts Rugh ◽  
Erica Grupp
Keyword(s):  
Sexual Activity ◽  
Litter Size ◽  
Normal Control ◽  
Lethal Effect ◽  
Whole Body ◽  
Sexually Active ◽  
X Rays ◽  
Male Mice ◽  
Adequate Number ◽  
X Irradiation

Sixty CF1 mice were given 600 r whole body x-irradiation, a dose calculated to kill 30% in 30 days. Half were isolated as controls and the remaining half were provided with an adequate number of nonpregnant, mature females for daily matings for the next 30 days. The controls showed 33% lethality while the experimentals, aggravated by frequent sexual activity, showed 73% lethality. Sexual activity more than doubled the lethal effect of 600 r x-rays. Litters derived from x-irradiated, sexually active males mated during the 1st week resulted in an average of 3.1; matings during the 2nd week produced an average of 2.7 (normal control size is 9.6). Matings during weeks 3–7 were sterile. Fertility was recovered by some at 8 weeks (litter size, 6.9) and by some as late as 75 days. Control x-irradiated males, after resumption of fertility, produced litters of 7.3.

Phospholipase Cβ1 (PLCβ1)-positive neurons in the brain are activated during sexual behavior in male mice

2006 ◽  
Vol 27 (1) ◽  
pp. 146 ◽  
Author(s):  
Alison J. Douglas ◽  
Katie Lunn ◽  
Peter Kind ◽  
Norah Spears
Keyword(s):  
Sexual Behavior ◽  
Male Mice ◽  
The Brain
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