Expression of Apelin and Apelin Receptor Protein in the Hypothalamo-Pituitary-Ovarian Axis during the Estrous Cycle of Mice

Abstract

Introduction: Apelin is an endogenous peptide, whose expression has been shown in the hypothalamus, pituitary, and ovary; furthermore, it is also called a neuropeptide, binding to apelin receptor (APJ) for various functions. It has been suggested that the hypothalamus, pituitary, and ovarian (HPO) axis is tightly regulated and factors and functions of the HPO axis can be modulated during the estrous cycle to influence reproductive status. To the best of our knowledge, the status of apelin and its receptor, APJ has not been investigated in the HPO axis during the estrous cycle. Methods: To explore the expression of apelin and APJ in the HPO axis of mice during the estrous cycle, mice were divided into four groups: proestrus (Pro), estrus (Est), metestrus (Met), and diestrus (Di), and apelin and APJ were checked. Further, to explore the role of apelin in gonadotropin secretion, an in vitro study of the pituitary was performed at the Pro and Est stages. Result: The expression apelin and APJ in the hypothalamus showed elevation during the estrous cycle of postovulatory phases, Met, and Di. The immunolocalization of apelin and APJ in the anterior pituitary showed more abundance in the Est and Di. Our in vitro results showed that gonadotropin-releasing hormone agonist stimulated luteinizing hormone secretion was suppressed by the apelin 13 peptide from the pituitary of Pro and Est phases. This suggests an inhibitory role of apelin on gonadotropin secretion. The ovary also showed conspicuous changes in the presence of apelin and APJ during the estrous cycle. The expression of apelin and APJ coincides with folliculogenesis and corpus luteum formation and the expression of the apelin system in the different cell types of the ovary suggests its cell-specific role. Previous studies also showed that apelin has a stimulatory role in ovarian steroid secretion, proliferation, and corpus luteum. Conclusion: Overall our results showed that the apelin system changes along the HPO axis during the estrous cycle and might have an inhibitory at level of hypothalamus and pituitary and a stimulatory role at ovarian level.