Jørgensen, Sara Rubek1; Andersen, Mille Dahl1; Overgaard, Agnete1; Mikkelsen, Jens D1
1 Neurologisk Klinik, Neurocentret, Rigshospitalet, The Capital Region of Denmark
Gonadotropin releasing hormone (GnRH) is a key player in the hypothalamic control of gonadotropin secretion from the anterior pituitary gland. It has been shown that the mammalian counterpart of the avian gonadotropin inhibitory hormone named RFamide-related peptide (RFRP) is expressed in hypothalamic neurons that innervate and inhibit GnRH neurons. The RFRP precursor is processed into two mature peptides RFRP-1 and RFRP-3. These are characterized by a conserved C-terminal motif Arg-Phe-NH2 but display highly different N-terminals. Even though the two peptides are equally potent in vitro, little is known about their relative distribution and their distinct roles in vivo. In this study, we raised an antiserum selective for RFRP-1 and defined the distribution of RFRP-1-immunoreactive (ir) neurons in the rat brain. Next, we analyzed the level of RFRP-1-immunoreactivity during postnatal development in males and females and investigated changes in RFRP-1-immunoreactivity during the estrous cycle. RFRP-1-ir neurons were distributed along the third ventricle from the caudal part of the medial anterior hypothalamus throughout the medial tuberal hypothalamus and were localized in, but mostly in between, the dorsomedial hypothalamic, ventromedial hypothalamic, and arcuate nuclei. The number of RFRP-1-ir neurons and the density of cellular immunoreactivity were unchanged from juvenile to adulthood in male rats during the postnatal development. However, both parameters were significantly increased in female rats from peri-puberty to adulthood, demonstrating prominent gender difference in the developmental control of RFRP-1 expression. The percentage of c-Fos positive RFRP-1-ir neurons was significantly higher in diestrus as compared to proestrus and estrus. In conclusion, we found that adult females, as compared to males, have significantly more RFRP-1-immunoreactivity pr cell, and these cells are regulated during the estrous cycle.
Endocrinology, 2014, Vol 155, Issue 11, p. 4402-10