Seasonal changes in RFamide‐related peptide‐3 neurons in the hypothalamus of a seasonally breeding marsupial species, the brushtail possum (Trichosurus vulpecula)

Abstract

RFamide-related peptide-3 (RFRP-3) neurons have been shown to inhibit gonadotropin-releasing hormone (GnRH) neuronal activity and hence reproduction in birds and eutherian mammals. They have also been proposed to have a direct hypophysiotropic effect on pituitary gonadotropin release. We used a new RFRP-3 antibody to characterize the cell body distribution and fiber projections of RFRP-3 neurons in the adult female brushtail possum brain. RFRP-3-immunoreactive cell bodies were found scattered within the dorsomedial hypothalamus and the dorsomedial half of the ventromedial hypothalamus, while GnRH neurons were observed scattered rostrocaudally along the lateral septum, rostral to the medial septum. There was a significant 2-fold increase in the RFRP-3 cell body number during the nonbreeding season (summer) compared to the breeding season (winter). Immunoreactive RFRP-3 fibers were distributed throughout the thalamus, preoptic area, and hypothalamus. Very few fibers were observed in the median eminence, especially in the external zone. Intraperitoneal injection of the retrograde tracer Fluoro-Gold resulted in the labeling of 40% of hypophysiotropic tuberoinfundibular dopaminergic (tyrosine hydroxylase-positive) neurons; however, <10% of zona incerta dopaminergic neurons (which are not hypophysiotropic) or RFRP-3 neurons were labeled with this tracer. These observations suggest that RFRP-3 exhibits a seasonal fluctuation in cell numbers, as seen in sheep and birds, which is consistent with an increased inhibitory tone during the nonbreeding season. The lack of RFRP-3 fibers in the median eminence and of Fluoro-Gold uptake from the periphery imply that the actions of this peptide occur primarily centrally rather than at the anterior pituitary gland.

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

“…Our results mirror changes in inhibitory tone in other mammals, where RFRP-3 neurons are confined to the DMH, and stress and breeding season-related decreases in cell numbers have been described (27)(28)(29)(30)(31). In these and avian species, the DMH is both the sole site of RFRP-3 synthesis and a chief regulator of neuroendocrine, autonomic, and behavioral responses to stress (for review, see ref.…”

“…The greatest extent of RFRP-3/GnRH fiber colocalization was observed in the ME, where dense GnRH fiber networks were present in the external layer. Although heavy RFRP-ir was seen in the internal layer, projections to the external zone were scarce, suggesting limited hypophysiotrophism as in other mammalian species (14,16,27,(48)(49)(50)(51). Rather than acting on both the pituitary and GnRH neurons as its avian ortholog does (11,13,52,53), it is likely that RFRP-3 acts directly only on GnRH neurons to inhibit NMR reproductive function.…”

“…In particular, RFRP-3 is commonly elevated during the nonbreeding season and suppressed following exposure to stimulatory photoperiods (brushtail possum: ref. 27 (31,32), with effects of social cues (i.e., nesting site availability) on GnIH activity also demonstrated in birds (33).…”

Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

“…GnIH-ir neurons in the ventro/dorsomedial hypothalamus are approximately three-fold higher in sexually active male jerboa captured in the spring compared to sexually inactive autumn animals (Janati et al, 2013). On the other hand, in the adult female brushtail possum brain, there is a significant 2-fold increase in GnIH cell body number during the nonbreeding season (summer) compared to the breeding season (winter) (Harbid et al, 2013).…”

Seasonal control of gonadotropin-inhibitory hormone (GnIH) in birds and mammals

“…As in hamsters, photoperiodic changes in GnIH are not a result of altered sex steroids in sheep [96]. In another long-day breeder, the brushtail possum, GnIH cell numbers were increased during the summer, non-breeding season relative the breeding season in females [37]. Thus, in long (i.e., hamsters) and short (i.e., sheep, possum) day breeders, the photoperiodic regulation of GnIH is highly conserved and the downstream targets of the GnIH system diverged to accommodate long and short-day breeding strategies.…”