RFAMIDE PEPTIDES INTEGRATE THE EFFECT OF NUTRITION ON THE GONADOTROPIC AXIS OF THE GILT
2012 Annual Report
1a.Objectives (from AD-416):
1. To determine the mechanism through which secretion of luteinizing hormone is suppressed in the prepubertal gilt.
2. Determine the mechanism of inhibition of luteinizing hormone release directly from the anterior pituitary gland of the gilt.
3. Determine the mechanism through which nutrition regulates gonadotropic output of the hypothalamic-pituitary axis of the gilt.
1b.Approach (from AD-416):
On average, 20% of gilts fail to reach puberty and become pregnant. Lack of sufficient secretion of gonadotropin hormones (e.g. Luteinizing hormone; LH) from the pituitary gland is a prominent reason for delayed puberty of pigs. Mechanisms in the hypothalamus that control LH secretion in the gilt are not well understood, but nutrition is an important component. The project goal is to minimize reproductive failure of replacement gilts. The objective will be to establish the function of RFamide-related and kisspeptin peptides in the control of LH secretion of the pig and identify their role in integrating nutrition with the gonadotropic axis of the gilt. Our approach, using intracerebroventricular cannulation, will be to establish the central effects of RFamide-related peptides on secretion of LH in gilts (Aim I). We will determine the direct effect of RFamide-related peptides on LH release from the pituitary gland of the pig (Aim II), and identify the relationship between energy balance and kisspeptin neurons in the hypothalamus of the gilt (Aim III). The rationale is that this work will advance our understanding of the basic biological mechanisms that control gonadotropin secretion in the gilt. The proposed research is significant, therefore, because application of this new fundamental knowledge is expected to lead to development of new strategies to minimize reproductive failure and maximize fertility of replacement gilts. This in turn will increase reproductive efficiency and decrease the expense of pork production.
RFamide-related peptide-3 (RFRP-3), the purported mammalian gonadotropin-inhibitory hormone (GnIH), was administered to prepubertal ovariectomized (OVX) gilts. Contrary to the hypothesis, RFRP-3 did not suppress pulsatile release of luteinizing hormone (LH) in a significant or consistent manner when administered either peripherally or centrally over a range of doses. This may result because removal of the ovaries allowed other neural networks that are suppressed by prepubertal estrogen (e.g., kisspeptin) to be upregulated, which could support continued LH pulses through increased stimulation of gonadotropin-releasing hormone (GnRH) neurosecretory activity in the hypothalamus. Consequently, we will employ an alternative approach to test the hypothesis that GnIH contributes to suppression of LH pulses prior to puberty by administering the RFRP receptor antagonist RF9 to ovary intact prepubertal gilts. The RF9 antagonist has been synthesized and experiments are underway to test its effects on LH release. Additionally, we administered RFRP-3 to mature Chinese Meishan boars. Laboratory analysis to quantify LH in serum of these boars is ongoing, but testosterone has been quantified. We observed that RFRP-3 neither inhibited nor stimulated testosterone release in mature boars. This preliminary result indicates that RFRP-3 likely did not affect LH secretion in these boars; a result that would corroborate our finding in gilts.