Breeding status and social environment differentially affect the expression of sex steroid receptor and aromatase mRNA in the brain of female Damaraland mole-rats

Abstract

IntroductionThe Damaraland mole-rat (Fukomys damarensis) is a eusocial, subterranean mammal, which exhibits an extreme reproductive skew with a single female (queen) monopolizing reproduction in each colony. Non-reproductive females in the presence of the queen are physiologically suppressed to the extent that they are anovulatory. This blockade is thought to be caused by a disruption in the normal gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. In order to understand the underlying physiological mechanisms of reproductive suppression in subordinate females we studied the expression of steroid hormone receptors and the androgen-converting enzyme aromatase in forebrain regions involved in the control of reproductive behaviour in female breeders and non-breeders from intact colonies. Additionally, we included in our analysis females that experienced the release from social suppression by being removed from the presence of the queen.ResultsWe found expression of androgen receptor, estrogen receptor α and aromatase in several forebrain regions of female Damaraland mole-rats. Their distribution matches previous findings in other mammals. Quantification of the hybridisation signal revealed that queens had increased expression of androgen receptors compared to non-breeders and removed non-breeders in most brain regions examined, which include the medial preoptic area (MPOA), the principal nucleus of the bed nucleus of the stria terminalis (BSTp), the ventromedial nucleus of the hypothalamus (VMH), the arcuate nucleus (ARC) and the medial amygdala (MeA). Furthermore, breeders had increased estrogen receptor α expression in the anteroventral periventricular nucleus (AVPV) and in the MeA, while aromatase expression in the AVPV was significantly reduced compared to non-breeders. Absence of social suppression was associated with increased androgen receptor expression in the ARC, increased estrogen receptor α expression in the MeA and BSTp and reduced aromatase expression in the AVPV.ConclusionThis study shows that social suppression and breeding differentially affect the neuroendocrine phenotype of female Damaraland mole-rats. The differential expression pattern of estrogen receptor α and aromatase in the AVPV between breeders and non-breeders supports the view that this region plays an important role in mediating the physiological suppression in subordinate females.

Neonatal amygdalae and hippocampi are influenced by genotype and prenatal environment, and reflected in the neonatal DNA methylome

“…90 To our knowledge, the interaction of estrogen action and SES on brain development has not been previously studied. However, because social status regulates ESR1 expression in model systems and is associated with altered limbic development, 91,92 an interaction of the same in human development seems credible. The association was strongest when tested across both genders (P-value for rs3020365 × SES = 4.71 × 10 −5 , R 2 overall = 0.17, where gender is a covariate in the model but not significant), when the data was segregated by gender, the association remained significant in males (P-value = 0.03, R 2 = 0.11) but was no longer significant in females.…”

Expression of aromatase in the rostral ventromedial medulla and its role in the regulation of visceral pain

“…Circulating estrogens are primarily made in the ovaries and the variation in circulating estrogen level likely accounts for the gender differences in pain and analgesia as well as the variation of pain symptom across the estrous cycle in female subjects . In addition to the peripheral sources of estrogens which may impact on neuronal regulation of pain, many areas in the CNS such as the hypothalamus, the amygdala, and the hippocampus are known to be capable of locally synthesizing estrogens from cholesterol . Therefore, it is possible that locally synthesized estrogens in discrete regions of the pain pathways may impact on pain and analgesia.…”

“…[31][32][33] In addition to the peripheral sources of estrogens which may impact on neuronal regulation of pain, many areas in the CNS such as the hypothalamus, the amygdala, and the hippocampus are known to be capable of locally synthesizing estrogens from cholesterol. [16][17][18][19][20][34][35][36] Therefore, it is possible that locally synthesized estrogens in discrete regions of the pain pathways may impact on pain and analgesia. Consistent with this notion, there have been reports demonstrating the expression of aromatase, the key enzyme responsible for the conversion of testosterone to estradiols, in areas important for the ascending transmission of pain signals, such as the dorsal horn of the spinal cord and the nucleus of the solitary tract.…”

Reproductive status affects the expression of prolactin receptor mRNA in the brain of female Damaraland mole-rats

“…The expression of prolactin receptor in brain sections was detected with antisense RNA probes labeled with 35 S-CTP as described before (Voigt et al 2014). Labeling of the probes with 35 S-CTP (1250 Ci/mmol; Perkin Elmer, Rodgau, Germany) was performed using the Riboprobe System (Promega).…”

“…In Damaraland mole-rats we have previously shown that reproductive status affects the neuroendocrine phenotype of females with reproductively suppressed females having reduced gene expression of steroid hormone receptors in several preoptic-hypothalamic brain regions, including the AVPV and the ARC. Moreover, such females also exhibit reduced Kiss1 expression in the ARC compared to reproductively active females (Voigt et al 2014, Voigt and. In another highly social African mole-rat, the naked mole-rat (Heterocephalus glaber), transcriptome profiling revealed reduced expression of genes involved in dopamine metabolism in reproductively suppressed subordinate females, which remain in a pre-pubertal anovulatory state (Mulugeta et al 2017).…”