Time for Testosterone: The Suprachiasmatic Nucleus Gets Sexy

Hagenauer, Megan Hastings; Lee, Theresa

doi:10.1210/en.2011-0198

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…Among other rhythms, the SCN regulates circadian rhythms in gonadal hormone secretion, and in turn hormones feedback to influence SCN functions (Fernandez-Guasti et al, 2000; Karatsoreos et al, 2007a; Kashon et al, 1996). A role for gonadal hormones in the maturation of circadian rhythmicity has been suggested in rodents and in non-human primates (Hagenauer et al, 2011a; Hagenauer et al, 2011b; Hagenauer and Lee, 2011; Hummer et al, 2012; Melo et al, 2010; Sellix et al, 2013). In humans, there is a correlation between chronotype (morningness or eveningness) and circulating hormone concentrations during aging (Harman et al, 2001; Roenneberg et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

“…ARs have been observed in the SCN of several species, including mouse, ferret, and human (Hagenauer and Lee, 2011; Karatsoreos et al, 2007a), though there are species differences in their concentration and distribution (Jahan et al, 2015). In the mouse, these ARs are specifically localized in retinorecipient cells of the SCN core subregion (Iwahana et al, 2008; Karatsoreos et al, 2007a).…”

Section: Introductionmentioning

confidence: 99%

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Suprachiasmatic nucleus as the site of androgen action on circadian rhythms

Model

Butler

LeSauter

et al. 2015

Hormones and Behavior

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Androgens act widely in the body in both central and peripheral sites. Prior studies indicate that in the mouse, suprachiasmatic nucleus (SCN) cells bear androgen receptors (ARs). The SCN of the hypothalamus in mammals is the locus of a brain clock that regulates circadian rhythms in physiology and behavior. Gonadectomy results in reduced AR expression in the SCN and in marked lengthening of the period of free-running activity rhythms. Both responses are restored by systemic administration of androgens, but the site of action remains unknown. Our goal was to determine whether intracranial androgen implants targeted to the SCN are sufficient to restore the characteristic free-running period in gonadectomized male mice. The results indicate that hypothalamic implants of testosterone propionate in or very near the SCN produce both anatomical and behavioral effects, namely increased AR expression in the SCN and restored period of free-running locomotor activity. The effect of the implant on the period of the free-running locomotor rhythm is positively correlated with the amount of AR expression in the SCN. There is no such correlation of period change with amount of AR expression in other brain regions examined, namely the preoptic area, bed nucleus of the stria terminalis and premammillary nucleus. We conclude that the SCN is the site of action of androgen effects on the period of circadian activity rhythmicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Suprachiasmatic nucleus as the site of androgen action on circadian rhythms

Model

Butler

LeSauter

et al. 2015

Hormones and Behavior

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“…Spontaneous release is a secretion responding to endogenous homeostatic conditions. The suprachiasmatic nucleus (SCN) of the hypothalamus coordinates circadian rhythms in physiology and behaviour, including endocrine rhythms, and the relationship between testosterone and the SCN has been widely investigated . In addition, the SCN also regulates ultradian rhythm, which has a shorter phase than circadian rhythm .…”

Section: Discussionmentioning

confidence: 99%

Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours

Masugi-Tokita

Yoshida

Kageyama

et al. 2018

J Neuroendocrinology

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Metabotropic glutamate receptor subtype 7 (mGluR7) is one of the group III mGluRs, which are negatively coupled to adenylate cyclase via Gi/Go proteins and localised to presynaptic active zones of the mammalian central nervous system. We previously reported that mGluR7 is essential for intermale aggression and amygdala-dependent fear learning. To elucidate the role of mGluR7 in the neuroendocrine system, we performed biochemical analyses and found a significant reduction of testosterone levels in mGluR7 knockout (KO) mice. Testosterone replacement restored intermale aggressive behaviour in castrated wild-type mice to the level of gonadally intact wild-type mice. However, given the same dosage of testosterone replacement, mGluR7 KO mice showed almost no aggressive behaviour. These results indicate that reduction of plasma testosterone is unrelated to the deficit in intermale aggression in mGluR7 KO mice. Social investigating behaviour of intact mGluR7 KO mice also differed from that of wild-type mice; e.g. the KO mice showing less frequent anogenital sniffing and more frequent grooming behaviour. Testosterone replacement increased anogenital sniffing and grooming behaviour in castrated mGluR7 KO mice, while the differences were still present between castrated wild-type mice and KO mice after both underwent testosterone replacement. These results imply that reduction of plasma testosterone may partially inhibit social investigating behaviours in intact mGluR7 KO mice. Furthermore, castrated mGluR7 KO mice have smaller seminal vesicles than those of castrated wild-type mice, although seminal vesicle weights were normal in intact mice. These observations suggest that, besides testicular testosterone, some other hormone levels may be dysregulated in mGluR7 KO mice, and indicate a critical role of mGluR7 in the endocrine system. Taken together, our findings demonstrate that mGluR7 is essential for the regulation of the endocrine system, in addition to innate behaviours such as intermale aggression and fear response.

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“…(2002) have shown that clock-mutant males produce significantly fewer progeny, and release smaller quantities of sperm [20], whereas the studies of ARNTL knock-out mice have shown deficiencies in steroidogenesis [7], namely, male ARNTL KO mice had altered levels of reproductive hormones, indicating a defect in testicular Leydig cells. On the other hand, there is evidence that reproductive hormones directly influence the circadian system [21]; dysregulation of the either axis could therefore contribute to the reduced fertility. The circadian system influences testosterone production in humans, showing morning peaks and evening decrease [8], [9], [10].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variation in Circadian Rhythm Genes CLOCK and ARNTL as Risk Factor for Male Infertility

et al. 2013

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BackgroundThe circadian system has a major role in maintaining homeostasis and proper body functions including reproductive capacity. The aim of this study was to examine whether there is an association between genetic variability in the primary clock genes CLOCK and ARNTL and male infertility in humans.Methodology/Principal FindingsWe performed a case-control study, where we searched for an association between polymorphisms of CLOCK and ARNTL genes and male infertility in 961 Slovenian and Serbian Caucasian men. The study group consisted of 517 patients with idiopathic infertility and a control group of 444 fertile men. A statistically significant difference was found in genotype distribution between the two groups in the CLOCK gene: rs11932595 (p = 6·10−5, q = 4·10−4, OR equaled 1.9 with 95% CI 1.4–2.7), rs6811520 (p = 2·10−3, q = 8·10−3, OR = 1.7 with 95% CI 1.2–2.2) and rs6850524 (p = 0.01, q = 0.02, OR = 1.4 with 95% CI 1.1–1.9). Further analyses of haplotypes were consistent with genotyping results.Conclusions/SignificanceWe provide evidence that genetic variability in the CLOCK gene might be associated with male infertility warranting further confirmation and mechanistic investigations.

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Time for Testosterone: The Suprachiasmatic Nucleus Gets Sexy

Cited by 10 publications

References 33 publications

Suprachiasmatic nucleus as the site of androgen action on circadian rhythms

Suprachiasmatic nucleus as the site of androgen action on circadian rhythms

Metabotropic glutamate receptor subtype 7 has critical roles in regulation of the endocrine system and social behaviours

Genetic Variation in Circadian Rhythm Genes CLOCK and ARNTL as Risk Factor for Male Infertility

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