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Induction of GH, PRL, and TSHβ mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line

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Abstract

The functional development of pituitary cells depends on the expression of a combination of transcription factors and co-factors. Pituitary-specific transcription factor-1 (Pit-1) is required for the expression of growth hormone (GH), prolactin (PRL), and the thyroid-stimulating hormone β subunit (TSHβ) and acts synergistically with the estrogen receptor (ER) and GATA-binding protein 2 (GATA-2) to induce PRL and TSHβ expression, respectively. The glycoprotein hormone α subunit (αSU) is the first hormone to be expressed during pituitary development. In addition to being expressed in follicle-stimulating hormone, luteinizing hormone (LH), and TSH cells, αSU is reported to co-localize with GH in pituitary cells. These findings have led to the suggestion that the expression of Pit-1 in cells of the αSU-based gonadotropin cell lineage might also lead to the expression of GH. In this study, we transfected HP75 cells (derived from a human non-functioning pituitary adenoma that expressed αSU and LHβ) with Pit-1 by using an adenovirus FLAG-Pit-1 construct. Most of the transfected cells expressed GH mRNA, with fewer cells expressing PRL and TSHβ mRNA. The HP75 cells expressed the genes for ER and GATA-2, thus allowing their expression of GH, PRL, and TSHβ mRNA in response to Pit-1. These results support the hypothesis that GH can be induced in cells that possess an active αSU gene and shed light on the basic molecular mechanism that drives the development of GH, PRL, and TSHβ expression in the αSU-based gonadotroph lineage.

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Abbreviations

αSU:

glycoprotein hormone alpha subunit

GH:

growth hormone

PRL:

prolactin

TSH:

thyroid-stimulating hormone

POMC:

pro-opiomelanocortin

ACTH:

adrenocorticotropic hormone

FSH:

follicle-stimulating hormone

LH:

luteinizing hormone

Pit-1:

pituitary-specific transcription factor-1

ER:

estrogen receptor

Tpit:

pituitary cell-restricted T-box factor

NeuroD1:

neurogenic differentiation 1

SF-1:

steroidogenic factor 1

GATA-2:

GATA-binding protein 2

DAX1:

dosage-sensitive sex-reversal, adrenal hypoplasia congenital, X chromosome

Ptx1:

pituitary homeobox 1

LHX3:

LIM homeobox protein 3

Prop-1:

Prophet of Pit-1

GHRH-R:

growth hormone-releasing hormone receptor

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Authors and Affiliations

  1. Department of Pathology, Tokai University School of Medicine, Bohseidai Isehara Campus, Kanagawa, 259-1193, Japan

    Shunsuke Miyai, Susumu Takekoshi & Robert Yoshiyuki Osamura

  2. Department of Molecular Life Science, Tokai University School of Medicine, Kanagawa, Japan

    Shinichi Yoshimura

  3. Department of Internal Medicine, Kochi University School of Medicine, Kochi, Japan

    Yasumasa Iwasaki

  4. Department of Laboratory Medicine and Pathology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA

    Ricardo V. Lloyd

Authors
  1. Shunsuke Miyai

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  2. Shinichi Yoshimura

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  3. Yasumasa Iwasaki

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  4. Susumu Takekoshi

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  5. Ricardo V. Lloyd

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  6. Robert Yoshiyuki Osamura

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Corresponding author

Correspondence toRobert Yoshiyuki Osamura.

Additional information

This work was supported by Grants-in-Aid for Scientific Research Projects (B, 16390110) of the Ministry of Education Culture, Sports, Science, and Technology, Japan, and by the Research on Measures for Intractable Diseases Project of the Hypothalamo-Pituitary Dysfunction Research Group of the Ministry of Health, Labor and Welfare, Japan.

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Miyai, S., Yoshimura, S., Iwasaki, Y.et al. Induction of GH, PRL, and TSHβ mRNA by transfection of Pit-1 in a human pituitary adenoma-derived cell line.Cell Tissue Res322, 269–277 (2005). https://doi.org/10.1007/s00441-005-0033-z

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