Dataset Information

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.

SUBMITTER: Sanchez NS

PROVIDER: S-EPMC5728413 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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

Sanchez N S NS Quinn K E KE Ashley A K AK Ashley R L RL

Domestic animal endocrinology 20171028

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, CX ...[more]

PMID: 29157995

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Project description:Pituitary gland function is regulated by the activity of various transcription factors which control cell fate decisions leading to cellular differentiation and hormone production. FOXO1 is necessary for the proper timing of somatotrope differentiation and for somatotrope function, but the exact mechanism of action has yet to be elucidated. Recent data implicate FOXO1 in the regulation of genes important for somatotrope differentiation including Gh1, Neurod4, and Pou1f1. Previously, a mouse model with conditional deletion of Foxo1 from the developing pituitary gland displayed reduced Gh1 and Neurod4 transcripts as early as embryonic day 18.5. Additional data from adult animals with conditional deletion of both Foxo1 and Foxo3 from the pituitary gland have a similar reduction in Neurod4 and Gh1, as well as Pou1f1. To investigate the mechanism by which FOXO1 regulates pituitary gland gene expression and confirm in vivo findings, the somatotrope-like cell line, GH3, was treated with the FOXO1 inhibitor, AS1842856, for 24 hours at various concentrations. Neurod4 was the most severely affected genes with a dose-dependent reduction in transcript at inhibitor concentrations as low as 30 nM. Gh1 transcripts were significantly reduced at 300 nM. Pou1f1 expression was trending down at 3 microM inhibitor (p=0.066). Consistent with these findings, CRISPR/Cas9-mediated deletion of Foxo1 in GH3 cells significantly reduced expression of Gh1, Neurod4, but not Pou1f1. To elucidate the molecular mechanisms underlying the role of FOXO1 in somatotropes, ChIPseq was performed for FOXO1 in the GH3 cell line. This study identified novel FOXO1 binding sites associated with the Neurod4, Gh1, and Pou1f1 genes. The FOXO1 binding site in the Neurod4 gene exhibits enhancer activity in somatotrope-like cells, but not in gonadotrope-like or heterologous cells. These data strongly suggest FOXO1 directly contributes to the transcriptional control of genes important for somatotrope differentiation. These novel findings contribute to the much-needed understanding of pituitary cell fate decisions.

Dataset Information

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

Publications

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

Similar Datasets

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