Characterization of Somatotrope Cell Expansion in Response to GHRH in the Neonatal Mouse Pituitary

Richard L Gonigam, Karen E Weis, Xiyu Ge, Boyuan Yao, Qilin Zhang, Lori T Raetzman

Research output: Contribution to journalArticlepeer-review

Abstract

In humans and mice, loss-of-function mutations in growth hormone-releasing hormone receptor (GHRHR) cause isolated GH deficiency. The mutant GHRHR mouse model, GhrhrLit/Lit (LIT), exhibits loss of serum GH, but also fewer somatotropes. However, how loss of GHRH signaling affects expansion of stem and progenitor cells giving rise to GH-producing cells is unknown. LIT mice and wild-type littermates were examined for differences in proliferation and gene expression of pituitary lineage markers by quantitative reverse transcription polymerase chain reaction and immunohistochemistry at postnatal day 5 (p5) and 5 weeks. At p5, the LIT mouse shows a global decrease in pituitary proliferation measured by proliferation marker Ki67 and phospho-histone H3. This proliferative defect is seen in a pituitary cell expressing POU1F1 with or without GH. SOX9-positive progenitors show no changes in proliferation in p5 LIT mice. Additionally, the other POU1F1 lineage cells are not decreased in number; rather, we observe an increase in lactotrope cell population as well as messenger RNA for Tshb and Prl. In the 5-week LIT pituitary, the proliferative deficit in POU1F1-expressing cells observed neonatally persists, while the number and proliferative proportion of SOX9 cells do not appear changed. Treatment of cultured pituitary explants with GHRH promotes proliferation of POU1F1-expressing cells, but not GH-positive cells, in a mitogen-activated protein kinase-dependent manner. These findings indicate that hypothalamic GHRH targets proliferation of a POU1F1-positive cell, targeted to the somatotrope lineage, to fine tune their numbers.

Original languageEnglish (US)
JournalEndocrinology
Volume164
Issue number10
Early online dateAug 24 2023
DOIs
StatePublished - Aug 28 2023

Keywords

  • GHRH
  • pituitary
  • somatotrope
  • POU1F1
  • proliferation
  • GHRHR

ASJC Scopus subject areas

  • Endocrinology

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