C-Type Natriuretic Peptide and the Guanylyl Cyclase Receptors in the Rat Ovary are Modulated by the Estrous Cycle1

Abstract

We have previously shown that rat ovaries synthesize atrial natriuretic peptide (ANP) and express the cognate guanylyl cyclase (GC-A and GC-B) receptors for ANP. Since another natriuretic peptide, termed the C-type natriuretic peptide (CNP), can also interact with these receptors, we have investigated whether rat ovaries express CNP and if so, whether the concentration of this natriuretic peptide and the guanylyl-cyclase receptors are influenced by the estrous cycle. CNP mRNA was detected in rat ovaries using a reverse transcription (RT) polymerase chain reaction (PCR) strategy. RIA of ovarian extracts, obtained at the individual days of the estrous cycle, revealed the presence of immunoreactive CNP. The highest levels of CNP were detected at proestrus and were approximately 4-fold higher than the levels seen at any other stage of the cycle. GC-A and GC-B receptors were detected using quantitative autoradiography after application of either [125I]ANP or [125I]-tyr0CNP to sections of frozen ovaries. The highest specific binding of each radiolabeled ligand was seen in ovaries from proestrous animals. The GC-B receptors were localized to the membrana granulosa of developing ovarian follicles. Using quantitative PCR, we determined that levels of GC-A and GC-B mRNAs were highest in the ovaries of proestrous animals and were approximately 2- to 3-fold higher than the levels seen at diestrus. These findings demonstrate that a natriuretic peptide system, consisting of ligands and receptors, is present in the rat ovary. Since CNP and the GC receptors show coordinate estrous cycle-dependent variation with maximal expression at proestrus, we speculate that the natriuretic peptides may play an important role in either the development of ovulatory follicles or in the ovulatory process.

Oxytocin is a cardiovascular hormone

“…CNP originally isolated from porcine brain (26) and shown as a neurotransmitter is now considered an important component of peripheral tissues including vascular endothelium (29) and ovaries (30). The actions of CNP are different from those described for ANP and BNP.…”

Molecular characterisation and functional interrogation of a local natriuretic peptide system in rodent pituitaries, αT3-1 and LβT2 gonadotroph cells

“…As well as the profound effects on endochondral ossification, these models of disrupted CNP/GC-B pathways suggest potentially important roles of this system in pituitary and gonadal tissues as Npr2 K/K mice are GH deficient and exhibit female infertility (Tamura et al 2004). Further support for CNP as a regulator of reproductive function comes from several studies that have shown CNP to potently stimulate cGMP production in GNRH neurons (Olcese et al 1994), pituitary gonadotrophs (McArdle et al 1993), and endocrine cells of the testis, ovaries, placenta and uterus (Khurana & Pandey 1993, Huang et al 1996, Middendorff et al 1996, Acuff et al 1997, Jankowski et al 1997, Gutkowska et al 1999, Stepan et al 2001, Walther & Stepan 2004, implicating CNP function at all levels of the hypothalamo-pituitarygonadal (HPG) axis. Furthermore, cGMP is a useful pharmacological target in the treatment of male reproductive disorders (Rosen & McKenna 2002, Christ & Hodges 2006.…”

Dephosphorylation and inactivation of NPR2 guanylyl cyclase in granulosa cells contributes to the LH-induced decrease in cGMP that causes resumption of meiosis in rat oocytes

“…LH signaling is known to decrease the amount of CNP in rat and mouse ovaries (Jankowski et al, 1997;Kawamura et al, 2011;Liu et al, 2014) and in human and porcine follicular fluid (Kawamura et al, 2011;Zhang et al, 2014); the decrease in the levels of CNP is associated with a decrease in Nppc mRNA (Kawamura et al, 2011;Tsuji et al, 2012;Liu et al, 2014). However, in the mouse ovary, where the kinetics are best characterized, the CNP decrease is first detected at 2 h Liu et al, 2014), whereas the decrease in cGMP is detected at 15 to 20 min (Norris et al, 2010;Liu et al, 2014).…”