Hormonal regulation of natriuretic peptide system during induced ovarian follicular development in the rat

All components of the natriuretic peptide (NP) system have been found in th e ovary, The purpose of this study was to determine the hormonal regulation of the NP system during follicular growth and ovulation induced by gonadot ropins eCG and hCG. Ovarian membrane binding, before and after treatment, r evealed the presence of guanylyl cyclase-type receptors exclusively. Equine CC treatment increased B-max from 225 +/- 50 fmol/mg protein in control an imals to 354 +/- 51 fmol/mg protein, and additional hCG treatment increased it further to 492 +/- 130 fmol/mg protein (p < 0.05), without changing rec eptor affinity. The increased binding was consistent with increased ability of atrial natriuretic peptide(ANP) to activate guanylyl cyclase in the ova rian cells obtained from hormone-treated animals. In confirmation, autoradi ography of I-125-tyr degrees CNP and I-125-ANP binding to the rat ovary sho wed that both guanylyl cyclase CCA and GC-B receptor subtypes are localized to the granulosa cells of antral follicles. Quantitative analysis of GC-A and GC-B receptors by reverse transcription-polymerase chain reaction showe d that the expression level of both receptors started to increase at 2 h an d reached maximal levels at 6 h following eCG treatment. Increased levels o f GC-B mRNA were also observed 12 h after eCG injection. At 24 and 48 h the receptor levels were below basal. Stimulation of NP receptors by eCG was p aralleled by activation of both ovarian ANP and C-type natriuretic peptide (CNP) gene expression. ANP mRNA increased as early as ? h after eCG injecti on and remained elevated up to 6 h, CNP mRNA increased at 2 h after eCG inj ection, peaked (5-fold) at 6 h, and remained elevated 48 h later, a stage a t which follicular maturation continues. Incubation of ovaries with ANP sig nificantly decreased eCG-induced estradiol level, indicating the functional ity of the ovarian NP system. These results implicate the NP system in the induction and maintenance of fluid balance in the rapidly developing ovaria n follicle.