Rapid changes in brain estrogen concentration during male sexual behavior are site and stimulus specific

Classically, estrogens regulate male sexual behavior through effects initiated in the nucleus. However, neuroestrogens, i.e., estrogens locally produced in the brain, can act within minutes via membrane-initiated events. In male quail, rapid changes in brain aromatase activity occur after exposure to sexual stimuli. We report here that local extracellular estrogen concentrations measured by in vivo microdialysis increase during sexual interactions in a brain site- and stimulus-specific manner. Indeed, estrogen concentrations rose within 10 min of the initiation of sexual interaction with a female in the medial preoptic nucleus only, while visual access to a female led to an increase in estrogen concentrations only in the bed nucleus of the stria terminalis. These are the fastest fluctuations in local estrogen concentrations ever observed in the vertebrate brain. Their site and stimulus specificity strongly confirm the neuromodulatory function of neuroestrogens on behavior.

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

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.

Not One Sexual Double Standard but Two? Adolescents’ Attitudes About Appropriate Sexual Behavior

Popular belief holds that sexual behavior is evaluated more liberally for males than females. However, the assessment of this “sexual double standard” is controversial. Therefore, we investigated measurement equivalence of commonly used items to assess sexual double standards in previous research. Based on established measurement equivalence, we investigated whether adolescents endorsed a sexual double standard. Using data from 455 adolescents ( Mage = 14.51, SD = 0.64), confirmatory factor analyzes showed that the sexual double standard concept was measurement equivalent across sex, and partly across evaluations of the same and opposite sex. Factor analyzes demonstrated that there was not one, but two sexual double standards. Male adolescents evaluated male sexual behavior more liberally than female sexual behavior, but female adolescents evaluated female sexual behavior more liberally than male sexual behavior. This contradicts the traditional notion of the existence of one sexual double standard that favors male and suppresses female sexuality.

Brain Aromatase and the Regulation of Sexual Activity in Male Mice

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.

Cystic proliferation of embryonic germ stem cells is necessary to reproductive success and normal mating behavior in medaka

ABSTRACTThe production of an adequate number of gametes in both sexes is necessary for normal reproduction, for which the regulation of proliferation from early gonadal development to adulthood is key. Cystic proliferation of embryonic stem germ cells prior the onset of gametogenesis is an especially important step prior to the beginning of meiosis. However, in vertebrates, the molecular regulators of cystic proliferation remain unknown. Here, we report that ndrg1b, a member of the N-myc downstream regulated family, is an important regulator of cystic proliferation in medaka. We generated mutants of ndrg1b that led to a disruption of proliferation type II, independently of the TGF-β signaling pathway. This loss of cystic proliferation was observed from embryogenic to adult stages, impacting the success of gamete production and reproductive parameters such as spawning and fertilization. Interestingly, the depletion of cystic proliferation of the ndrg1b mutant also impacted male sexual behavior, with a decrease of mating vigor. These data illustrate why it is also necessary to consider gamete production capacity in order to analyze reproductive behavior.HIGHLIGHTSNdrg1b is involved in the regulation of cystic proliferation in gonad from embryo to adulthood.The cystic proliferation is independently of the TGF-β signaling pathway.Decrease of production of gametes declines reproductive success for both sexes.Reduction of cystic proliferation declines male sexual behavior, with a decrease of mating vigor.

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

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.

Regulation of olfactory-based sex behaviors in the silkworm by genes in the sex-determination cascade

Insect courtship and mating depend on integration of olfactory, visual, and tactile cues. Compared to other insects, Bombyx mori, the domesticated silkworm, has relatively simple sexual behaviors as it cannot fly. Here by using CRISPR/Cas and electrophysiological techniques we found that courtship and mating behaviors are regulated in male silk moths by mutating genes in the sex determination cascade belonging to two conserved pathways. Loss of Bmdsx gene expression significantly reduced the peripheral perception of the major pheromone component bombykol by reducing expression of the product of the BmOR1 gene which completely blocked courtship in adult males. Interestingly, we found that mating behavior was regulated independently by another sexual differentiation gene, Bmfru. Loss of Bmfru completely blocked mating, but males displayed normal courtship behavior. Lack of Bmfru expression significantly reduced the perception of the minor pheromone component bombykal due to the down regulation of BmOR3 expression; further, functional analysis revealed that loss of the product of BmOR3 played a key role in terminating male mating behavior. Our results suggest that Bmdsx and Bmfru are at the base of the two primary pathways that regulate olfactory-based sexual behavior.Author SummaryThe fundamental insect sexual behaviors, courtship and mating, result from successful integration of olfactory, vision, tactile and other complex innate behaviors. In the widely used insect model, Drosophila melanogaster, the sex determination cascade genes fruitless and doublesex are involved in the regulation of courtship and mating behaviors; however, little is known about the function of these sexual differentiation genes in regulating sex behaviors of Lepidoptera. Here we combine genetics and electrophysiology to investigate regulation pathway of sexual behaviors in the model lepidopteran insect, the domesticated silk moth, Bombyx mori. Our results support the presence of two genetic pathways in B. mori, named Bmdsx-BmOR1-bombykol and Bmfru-BmOR3-bombykal, which control distinct aspects of male sexual behavior that are modulated by olfaction. This is the first comprehensive report about the role of sex differentiation genes in the male sexual behavior in the silk moth.

Does HIV infection increase male sexual behavior?

After 40 years of intense study on HIV/AIDS, scientists have identified, among other things, at risk populations, stages of disease progression and treatment strategies. What has received less attention is the possibility that infection might elicit an increase in sexual behavior in humans. In 2000, Starks and colleagues speculated that HIV infection could alter host behavior in a manner that facilitated the spread of the virus. Retrospective and self-report data from five studies now support this hypothesis. Individuals with acute—versus nonacute—stage infections report more sexual partners and more frequent risky sex. Additionally, male sexual behavior increases nonlinearly with HIV viral load, and data suggest a potential threshold viral level above which individuals are more likely to engage in risky sexual behavior. Taken together, these data suggest that HIV infection influences male sexual behavior in a manner beneficial to the virus. Here, we present these findings, highlight their limitations and discuss alternative perspectives. We argue for increased testing of this hypothesis and advocate for increased public health measures to mitigate the putative impact on male sexual behavior. Lay Summary In 2000, Starks and colleagues speculated that HIV infection could alter host behavior in a manner that facilitated the spread of the virus. Retrospective and self-report data from five studies now support this hypothesis. We argue for increased testing of this hypothesis and advocate for increased public health measures to mitigate the putative impact on male sexual behavior.