Social status and sex independently influence androgen receptor expression in the eusocial naked mole-rat brain

Abstract

Naked mole-rats (Heterocephalus glaber) are eusocial rodents that live in large subterranean colonies including a single breeding female and 1-3 breeding males; all other members of the colony, known as subordinates, are reproductively suppressed. We recently found that naked mole-rats lack many of the sex differences in the brain and spinal cord commonly found in other rodents. Instead, neural morphology is influenced by breeding status, such that breeders, regardless of sex, have more neurons than subordinates in the ventromedial nucleus of the hypothalamus (VMH), and larger overall volumes of the bed nucleus of the stria terminalis (BST), paraventricular nucleus (PVN) and medial amygdala (MeA). To begin to understand how breeding status influences brain morphology, we examined the distribution of androgen receptor (AR) immunoreactivity in gonadally intact breeders and subordinates of both sexes. All animals had AR+ nuclei in many of the same regions positive for AR in other mammals, including the VMH, BST, PVN, MeA, and the ventral portion of the premammillary nucleus (PMv). We also observed diffuse labeling throughout the pre-optic area demonstrating that distribution of the AR protein in presumptive reproductive brain nuclei is wellconserved, even in a species that exhibits remarkably little sexual dimorphism. In contrast to other rodents, however, naked mole-rats lacked AR+ nuclei in the suprachiasmatic nucleus and hippocampus. Males had more AR+ nuclei in the MeA, VMH, and PMv than did females. Surprisingly, breeders had significantly fewer AR+ nuclei than subordinates in all brain regions examined (VMH, BST, PVN, MeA, and PMv). Thus, social status is strongly correlated with AR immunoreactivity in this eusocial species.

The Vertebrate mesolimbic reward system and social behavior network: A comparative synthesis

“…It is located in the hypothalamus conspicuously along the third ventricle and ventral to the anterior commissure. It mediates aggression, sexual behavior, and parental care (Table 1) (Heimer and Larsson, 1967;Malsbury, 1971;Hull and Dominguez, 2006;Lee and Brown, 2007), and contains tyrosine hydroxylase (TH)-and neuropeptide-expressing cells as well as sex steroid receptors (Wang et al, 1996;Rosen et al, 2007;Holmes et al, 2008). It is reciprocally connected to many limbic brain regions, especially those in the SBN (Conrad and Pfaff, 1975).…”

“…The VMH is topographically located in the caudal hypothalamus along the third ventricle, is rich with sex steroid receptors (Zhang et al, 2002;Lonstein and Blaustein, 2004;Holmes et al, 2008), and is highly interconnected with the amygdala and other regions of the hypothalamus (Saper et al, 1976). The best understood function of the VMH in social behavior is its central role in regulating female receptivity.…”

Social regulation of adult neurogenesis in a eusocial mammal

“…Likewise, colonyhoused subordinates may become breeders if sexual suppression is lifted by a former breeder's death or removal (Margulis et al, 1995;Clarke and Faulkes, 1997). Though pronounced alterations in neural and endocrine functions accompany the change (Faulkes et al, 1990a;Margulis et al, 1995;Clarke and Faulkes, 1997;Seney et al, 2006;Holmes et al, 2008;Holmes et al, 2011;Mooney and Holmes, 2013), many or all subordinates are capable of transitioning to breeding status under the appropriate social conditions. This striking behavioural and physiological plasticity displayed by otherwise mature subordinates makes the naked mole-rat a prime candidate for the study of adult neurogenesis.…”

Winning territorial disputes selectively enhances androgen sensitivity in neural pathways related to motivation and social aggression

“…We also speculate that such changes occur only after wins in the home territory and not in unfamiliar locations. These hypotheses are rooted in studies that show that changes in neural steroid receptors are sensitive to social stimuli (12,13) and that testosterone and progesterone impact expression of androgen and progestin receptors (AR and PR) (14,15). We explored the issues described above by providing male California mice with winning experiences in either their home or unfamiliar cages and then using immunocytochemistry to test if these experiences affected neural AR or PR.…”