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成年垂体中的 hedgehog 信号在内分泌细胞和滤泡星状细胞中的作用。

Hedgehog signaling in endocrine and folliculo-stellate cells of the adult pituitary.

机构信息

Institute of Human Genetics, Molecular Developmental Genetics and Tumor Genetics Group, University Medical Center, Göttingen, Germany.

Institute of Pathology, Sozialstiftung Bamberg, Klinikum am Bruderwald, Bamberg, Germany.

出版信息

J Endocrinol. 2021 Mar;248(3):303-316. doi: 10.1530/JOE-20-0388.

DOI:10.1530/JOE-20-0388
PMID:33480359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7983331/
Abstract

Ubiquitous overactivation of Hedgehog signaling in adult pituitaries results in increased expression of proopiomelanocortin (Pomc), growth hormone (Gh) and prolactin (Prl), elevated adrenocorticotropic hormone (Acth) production and proliferation of Sox2+ cells. Moreover, ACTH, GH and PRL-expressing human pituitary adenomas strongly express the Hedgehog target GLI1. Accordingly, Hedgehog signaling seems to play an important role in pathology and probably also in homeostasis of the adult hypophysis. However, the specific Hedgehog-responsive pituitary cell type has not yet been identified. We here investigated the Hedgehog pathway activation status and the effects of deregulated Hedgehog signaling cell-specifically in endocrine and non-endocrine pituitary cells. We demonstrate that Hedgehog signaling is unimportant for the homeostasis of corticotrophs, whereas it is active in subpopulations of somatotrophs and folliculo-stellate cells in vivo. Reinforcement of Hedgehog signaling activity in folliculo-stellate cells stimulates growth hormone production/release from somatotrophs in a paracrine manner, which most likely is mediated by the neuropeptide vasoactive intestinal peptide. Overall, our data show that Hedgehog signaling affects the homeostasis of pituitary hormone production via folliculo-stellate cell-mediated regulation of growth hormone production/secretion.

摘要

Hedgehog 信号在成人垂体中的普遍过度激活导致前阿黑皮素原（Pomc）、生长激素（Gh）和催乳素（Prl）的表达增加，促肾上腺皮质激素（Acth）的产生增加，Sox2+细胞增殖。此外，表达 ACTH、GH 和 PRL 的人类垂体腺瘤强烈表达 Hedgehog 靶基因 GLI1。因此，Hedgehog 信号似乎在病理学中发挥重要作用，可能在成人垂体的稳态中也发挥作用。然而，特定的 Hedgehog 反应性垂体细胞类型尚未确定。我们在这里研究了 Hedgehog 通路的激活状态以及 Hedgehog 信号的失调对内分泌和非内分泌垂体细胞的特异性影响。我们证明 Hedgehog 信号对促肾上腺皮质激素细胞的稳态不重要，而在体内生长激素细胞和滤泡星形细胞的亚群中是活跃的。Hedgehog 信号活性在滤泡星形细胞中的增强以旁分泌的方式刺激生长激素从生长激素细胞中的产生/释放，这很可能是由神经肽血管活性肠肽介导的。总的来说，我们的数据表明 Hedgehog 信号通过滤泡星形细胞介导的生长激素产生/分泌的调节来影响垂体激素产生的稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/76233d78f9a2/JOE-20-0388fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/f3313a347e1d/JOE-20-0388fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/95ff28e1fa2f/JOE-20-0388fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/fdc447256b45/JOE-20-0388fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/98471804404c/JOE-20-0388fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/4a710b4a91ac/JOE-20-0388fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/837e4f11deac/JOE-20-0388fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/76233d78f9a2/JOE-20-0388fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/f3313a347e1d/JOE-20-0388fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/95ff28e1fa2f/JOE-20-0388fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/fdc447256b45/JOE-20-0388fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/98471804404c/JOE-20-0388fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/4a710b4a91ac/JOE-20-0388fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/837e4f11deac/JOE-20-0388fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/caae/7983331/76233d78f9a2/JOE-20-0388fig7.jpg

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