Novel mechanisms for DHEA action

Prough, Russell A.; Clark, Barbara J.; Klinge, Carolyn M.

doi:10.1530/jme-16-0013

Cited by 134 publications

(98 citation statements)

References 142 publications

(173 reference statements)

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“…, see also: Soma & Wingfield ; Demas, Soma & Albers ; Soma et al . ; Prough, Clark & Klinge ; Rendon & Demas ). DHEA can serve as a precursor to testosterone and oestradiol, therefore metabolic conversion makes it possible for relatively low levels of circulating hormones to have dynamic behavioural effects across seasons, as observed across numerous mammals and birds (Hau, Stoddard & Soma ; Soma et al .…”

Section: Discussionmentioning

confidence: 99%

“…Marked increases in aggression occur during gonadal regression when oestradiol secretion is basal, suggesting that short-day aggression is independent of oestradiol or that these animals rely on another hormonal precursor to regulate aggression. In support of the latter hypothesis, we have recently shown that adrenal androgen dehydroepiandrosterone (DHEA) concentrations mirror seasonal aggression (Rendon et al 2015b) and that the adrenal gland is a key hormonal source during periods of reproductive quiescence, indicative of a 'seasonal switch' from gonadal to adrenal regulation of aggression (Rendon et al 2015b, see also: Soma & Wingfield 1999;Demas, Soma & Albers 2011;Soma et al 2015;Prough, Clark & Klinge 2016;. DHEA can serve as a precursor to testosterone and oestradiol, therefore metabolic conversion makes it possible for relatively low levels of circulating hormones to have dynamic behavioural effects across seasons, as observed across numerous mammals and birds (Hau, Stoddard & Soma 2004;Soma et al 2005Soma et al , 2015Labrie 2010Labrie , 2015Pradhan et al 2010;Demas, Soma & Albers 2011).…”

Section: A L T E R N a T I V E S O U R C E S O F O E S T R A D I O L mentioning

confidence: 93%

“…This inconsistency in oestradiol warrants further examination (see Phalen et al 2010), however, the hypothesis that aggression during short days is independent of circulating hormones is supported. Although the precise mechanisms underlying seasonal aggression are not fully known, future studies should address the potential interplay between melatonin and hormonal profiles, the role of brain-derived steroids, nongenomic responses to hormones and seasonal shifts in receptor affinity (do Rego & Vaudry 2015;Soma et al 2015;Prough, Clark & Klinge 2016). Additional neuroendocrine mechanisms may be involved in the regulation of aggression across seasonal transitions [e.g.…”

Section: A L T E R N a T I V E S O U R C E S O F O E S T R A D I O L mentioning

confidence: 99%

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Aggressive behaviours track transitions in seasonal phenotypes of female Siberian hamsters

et al. 2017

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SUMMARY Seasonally breeding animals exhibit profound physiological and behavioural responses to changes in ambient day length (photoperiod), including changes in reproductive function and territorial aggression. Species where aggression persists when gonads are regressed and circulating levels of gonadal hormones are low, such as Siberian hamsters (Phodopus sungorus) and song sparrows (Melospiza melodia), challenge the well-established framework that gonadal hormones are important mediators of aggression. A solution to this apparent paradox is that a season-specific increase in sensitivity to hormones in brain areas associated with aggression offsets low levels of gonadal hormones during periods of reproductive quiescence. To test this hypothesis, we manipulated photoperiod to induce natural fluctuations in seasonal phenotype across multiple stages of the annual reproductive cycle in female Siberian hamsters that display increased aggression during short-day reproductive quiescence, suggesting that behaviour persists independent of gonadal steroids. Females were housed in long “summer” days or short “winter” days for 10, 24 or 30 weeks to capture gonadal regression, transition back to a reproductively functional state and full gonadal recrudescence, respectively. Long-day animals maintained reproductive functionality and displayed low aggression across all time points. By week 10, short-day reproductively responsive females underwent gonadal regression and displayed increased aggression; non-responsive animals showed no such changes. At week 24, animals were in a transitional period and displayed an intermediate phenotype with respect to reproduction and aggression. By week 30, short-day females were fully recrudesced and returned to long-day-like levels of aggression. Consistent with our hypothesis, gonadally regressed females displayed decreases in 17β-oestradiol (oestradiol) levels, but site-specific increases in the abundance of brain oestrogen receptor-alpha (ERα) in regions associated with aggression, but not reproduction. Increased site-specific ERα may function as a compensatory mechanism to allow increased responsiveness to oestradiol in regulating aggression in lieu of high circulating concentrations of hormones. Collectively, these results broaden our understanding of how breeding phenology maps onto social behaviour and the mechanisms that have evolved to coordinate behaviours that occur in non-breeding contexts.

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Section: Discussionmentioning

confidence: 99%

Section: A L T E R N a T I V E S O U R C E S O F O E S T R A D I O L mentioning

confidence: 93%

Section: A L T E R N a T I V E S O U R C E S O F O E S T R A D I O L mentioning

confidence: 99%

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Aggressive behaviours track transitions in seasonal phenotypes of female Siberian hamsters

et al. 2017

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“…Whether this steroid performs a similar function in the human fetus remains to be determined. DHEA has also been shown to be a ligand for many hepatic nuclear receptors and G-protein-coupled receptors (35). …”

Section: Discussionmentioning

confidence: 99%

Androgenic potential of human fetal adrenals at the end of the first trimester

Savchuk

Morvan

Antignac

et al. 2017

Endocrine Connections

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The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9–12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry. The expression of steroidogenic enzymes and transcription factors in the HFA at GW9–12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that during GW9–12 HFA produced steroids of the ∆5, ∆4 and the backdoor pathways of the biosynthesis of DHT, though the latter was limited to production of 17α-OH-dihydroprogesterone, androsterone and androstanedione without further conversion to DHT. The only androgens identified in the HFA were testosterone and androsterone, a precursor in the biosynthesis of DHT. We also observed higher levels of CYP17A1 but low expression of 3βHSD2 at GW11–12 in the HFA. Elevated levels of CYP17A1 were associated with an increased expression of SF-1 and GATA-6. Altogether, our data demonstrate that of those steroids analyzed, the only potent androgen directly produced by the HFA at GW9–12 was testosterone. The onset of steroidogenesis in the HFA is a complex process that is regulated by the coordinated action of related transcription factors.

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“…111 DHEA is also believed to have endocrine functions that are independent of its conversion to potent sex steroids. 112 Clinical adrenarche is described as premature if it occurs before 8 years of age in girls and 9 years in boys. 109 Premature adrenarche could be caused by either an early onset of adrenal androgen synthesis, with a subsequent "normal" rate of increase, or an onset at the same age but with accelerated increase in production.…”

Section: Box 2 Adrenarchementioning

confidence: 99%

The tempo of human childhood: a maternal foot on the accelerator, a paternal foot on the brake

Kotler¹,

Haig

2018

Evolutionary Anthropology

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Relative to the life history of other great apes, that of humans is characterized by early weaning and short interbirth intervals (IBIs). We propose that in modern humans, birth until adrenarche, or the rise in adrenal androgens, developmentally corresponds to the period from birth until weaning in great apes and ancestral hominins. According to this hypothesis, humans achieved short IBIs by subdividing ancestral infancy into a nurseling phase, during which offspring fed at the breast, and a weanling phase, during which offspring fed specially prepared foods. Imprinted genes influence the timing of human weaning and adrenarche, with paternally expressed genes promoting delays in childhood maturation and maternally expressed genes promoting accelerated maturation. These observations suggest that the tempo of human development has been shaped by consequences for the fitness of kin, with faster development increasing maternal fitness at a cost to child fitness. The effects of imprinted genes suggest that the duration of the juvenile period (adrenarche until puberty) has also been shaped by evolutionary conflicts within the family.

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Novel mechanisms for DHEA action

Cited by 134 publications

References 142 publications

Aggressive behaviours track transitions in seasonal phenotypes of female Siberian hamsters

Aggressive behaviours track transitions in seasonal phenotypes of female Siberian hamsters

Androgenic potential of human fetal adrenals at the end of the first trimester

The tempo of human childhood: a maternal foot on the accelerator, a paternal foot on the brake

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