Gonadal Steroid Induction of Kisspeptin Peptide Expression in the Rostral Periventricular Area of the Third Ventricle During Postnatal Development in the Male Mouse

Abstract

Kisspeptin and its G-protein coupled receptor Gpr54 are essential for the pubertal activation of gonadotrophin-releasing hormone (GnRH) neurones, with Gpr54 mutation or deletion resulting in failed puberty and infertility in humans and mice. The number of kisspeptin-immunoreactive neurones in the rostral periventricular area of the third ventricle (RP3V) increases during pubertal development in concert with the appearance of kisspeptin appositions with GnRH neurones in the mouse rostral preoptic area. We recently demonstrated that the pubertal increase in RP3V kisspeptin neuronal number in females is dependent upon circulating oestradiol levels. The present experiments investigated the potential role of gonadal steroids in the induction of kisspeptin expression in the RP3V during pubertal development in the male mouse. Using immunocytochemistry (ICC), we show that gonadectomy of male pups at postnatal day (P) 20 resulted in a 60-70% reduction in the number of kisspeptin immunoreactive (IR) neurones within the RP3V of P45 mice (P<0.05) compared to sham-treated littermates. We established a profile of circulating testosterone levels during postnatal development in male mice and found that circulating testosterone was low throughout early postnatal development and increased from P35-40 to reach adult levels. Treatment of P20-gonadectomised male mice with 17β-oestradiol or testosterone from P38-45 restored kisspeptin-IR neurone number in the RP3V to intact control levels (P>0.05). Using double-label ICC, we demonstrate that the majority of RP3V kisspeptin neurones express androgen receptors and oestrogen receptor α, indicating that RP3V kisspeptin neurones in the male mouse are equipped to respond to both androgen and oestrogen signals. These results indicate that, as in females, gonadal steroids are essential for the increase in kisspeptin immunoreactive cell number that occurs in the RP3V during pubertal development in the male mouse.

A Critical Point of Male Gonad Development: Neuroendocrine Correlates of Accelerated Testicular Growth in Rats during Early Life

“…The developmental profile of kisspeptin mRNA obtained in our study with real-time PCR is in agreement with previous data [44] and well coincides with immunohistochemical identification of kisspeptin expression. During the first 2 weeks of life, low-level immunoreactivity for kiss-1 was detected in the male rat arcuate nucleus [45]. Though mice lacking kisspeptin-Kiss1r signaling had smaller testes already at postnatal day 10 [21], kisspeptin or its receptor mRNA levels in the present study did not correlate with testis weights during the periods of the proportional and accelerated growth of the gonads.…”

Neuroanatomy of the Kisspeptin Signaling System in Mammals: Comparative and Developmental Aspects

“…While cell numbers in the RP3V of male rodents are much lower than that for females (discussed below), Han et al (13) showed that the number of cells expressing kisspeptin mRNA was greater in adults than juveniles and that expression level per cell increased as well. Clarkson and Herbison (11) reported that kisspeptin-positive cell numbers began to increase at PND 25 and peaked at PND 45, but these changes may reflect increased circulating levels of gonadal steroids since they were abolished by gonadectomy at PND 20 and restored to normal with either testosterone or estradiol treatment (138). In contrast, others have reported very low cell numbers with no change (50;126) or only small changes (128) in the RP3V.…”

Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

“…One explanation is that wildtype males are not exposed to increasing testosterone (converted to estradiol) during the postnatal period from P2 to P28. The testosterone surge (1.6–1.7 ng/mL) at 1–2 hours after birth is followed by a drop in the level of testosterone (0.04 to 0.6 ng/mL) on days P2-P30 [31, 32, 34]. The increase in testosterone starts about P35 (0.9 ng/mL) and continues to rise by P40 (2.1 ng/mL), which is early puberty for males.…”