In the ovine pituitary, CXCR4 is localized in gonadotropes and somatotropes and increases with elevated serum progesterone

Abstract

The pituitary is the central endocrine regulator of reproduction and in addition to various hormones regulating its actions, other molecules, such as chemokines, influence pituitary physiology as well. Despite reports over 2 decades ago that chemokines regulate the pituitary, much of the basic biology discerning chemokine action in the pituitary is unclear. A small number of chemokines and their receptors have been localized to the pituitary, yet chemokine ligand 12 (CXCL12) and its receptor, CXCR4, have received the most attention as both are increased in human pituitary adenomas. This chemokine duo was also reported in normal human and rat pituitary, suggestive of a functional role and that this chemokine axis might function in pituitaries from other mammalian species. To date, reports of CXCL12 and CXCR4 in pituitary from livestock are lacking, and research on pituitary during pregnancy in any mammalian species is limited. Moreover, progesterone regulates CXCR4 expression in a tissue-dependent manner, but whether differing concentrations of progesterone reaching the pituitary modulate CXCL12 or CXCR4 is not known. To address these gaps, our first objective was to determine if CXCL12 and CXCR4 expression and protein abundance differ in sheep pituitary during early gestation (days 20, 25, and 30 of gestation) compared to nonpregnant ewes. The second objective was to determine if CXCL12 or CXCR4 production was altered in the ovine pituitary when circulating progesterone concentrations are elevated. The expression of CXCL12 messenger RNA decreased on day 20 of gestation compared to nonpregnant ewes; CXCL12 protein was similar across all days tested. In nonpregnant and pregnant ewes, CXCR4 was localized to somatotropes and gonadotropes on all days tested. Abundance of CXCR4 increased in the pituitary tissue of pregnant ewes with elevated circulating progesterone compared with pregnant ewes with normal circulating progesterone concentrations (control). The present study details CXCL12 and CXCR4 in normal ovine pituitary and reveals that gonadotropes and somatotropes may be regulated by CXCL12/CXCR4, underscoring this signaling axis as a potential new class of modulator in endocrine functions.