Short-Chain Fatty Acids Inhibit Growth Hormone and Prolactin Gene Transcription via cAMP/PKA/CREB Signaling Pathway in Dairy Cow Anterior Pituitary Cells

Jian-Fa Wang,Zhi-Qiang Li,Bing-Xu Huang,Ju-Xiong Liu,Qing-Kang Lv,Wen-Jing Xue,Zhong-Ming Hu,Shou-Peng Fu,Su-Nan Li,Wei Wang

doi:10.3390/ijms141121474

Abstract

Short-chain fatty acids (SCFAs) play a key role in altering carbohydrate and lipid metabolism, influence endocrine pancreas activity, and as a precursor of ruminant milk fat. However, the effect and detailed mechanisms by which SCFAs mediate bovine growth hormone (GH) and prolactin (PRL) gene transcription remain unclear. In this study, we detected the effects of SCFAs (acetate, propionate, and butyrate) on the activity of the cAMP/PKA/CREB signaling pathway, GH, PRL, and Pit-1 gene transcription in dairy cow anterior pituitary cells (DCAPCs). The results showed that SCFAs decreased intracellular cAMP levels and a subsequent reduction in PKA activity. Inhibition of PKA activity decreased CREB phosphorylation, thereby inhibiting GH and PRL gene transcription. Furthermore, PTX blocked SCFAs- inhibited cAMP/PKA/CREB signaling pathway. These data showed that the inhibition of GH and PRL gene transcription induced by SCFAs is mediated by Gi activation and that propionate is more potent than acetate and butyrate in inhibiting GH and PRL gene transcription. In conclusion, this study identifies a biochemical mechanism for the regulation of SCFAs on bovine GH and PRL gene transcription in DCAPCs, which may serve as one of the factors that regulate pituitary function in accordance with dietary intake.

Highlights

The pituitary plays a critical role in animals and regulates a broad range of physiological processes involved in growth, metabolism, reproduction, lactation, and stress [1]
The transcription of the growth hormone (GH) and PRL gene were significantly higher in the pertussis toxin (PTX) + acetate group than in the 1.0 mmol/L acetate treatment group (Figure 1D; p < 0.05)
These results strongly suggest that SCFAs significantly down-regulate the expression of GH and PRL gene in dairy cow anterior pituitary cells (DCAPCs), and the mRNA levels of GH and PRL

Summary

Introduction

The pituitary plays a critical role in animals and regulates a broad range of physiological processes involved in growth, metabolism, reproduction, lactation, and stress [1]. Growth hormone (GH) is a polypeptide hormone synthesized and secreted by the anterior pituitary gland. It plays a key role in regulating ruminant mammary gland development and lactation [2]. Bovine GH induces proliferation of mammary parenchyma and growth of epithelial cells, and increase the cell renewal in the mammary gland [3]. Prolactin (PRL) is a polypeptide hormone that is synthesized in and secreted from lactotrophs of the anterior pituitary gland [6]. PRL play a key role in regulating mammary gland development and lactation [7]. Because of the irreplaceable regulatory role in growth, metabolism, and lactation, researches on endocrinology always focus on the factors and mechanisms affecting GH and PRL synthesis and release

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Conclusion