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

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.