Thyrotropin-releasing hormone inhibits GH4 pituitary cell proliferation by blocking entry into S phase

Endocrinology
J S Ramsdell

Abstract

TRH inhibits the proliferation of GH4 rat pituitary cells. We have characterized TRH inhibition of cell proliferation by four approaches: cell number, [3H]thymidine incorporation per culture, bromodeoxyuridine (BrdUrd) incorporation per cell, and cell cycle distribution. TRH decreases GH4 cell number within 18 h of treatment, and this inhibition is maintained for up to 96 h. TRH inhibits [3H]thymidine incorporation into GH4 cell cultures as early as 12 h, and the inhibition of [3H] thymidine incorporation correlates, after a 6-h lag, with decreased GH4 cell number. TRH inhibition of [3H]thymidine incorporation is concentration dependent and saturable, with half-maximal inhibition (IC50) of 2 nM. TRH inhibition of [3H] thymidine incorporation is receptor number dependent up to 160,000 sites/cell, suggesting no spare receptors for TRH on GH4C1 cells. The precise action of TRH on GH4 cell proliferation was examined by flow cytometry of fluorescein isothiocyanate-anti-BrdUrd- and propidium iodide-DNA stained cells. TRH inhibits the number of cells that incorporate BrdUrd and not the amount of BrdUrd incorporated per cell. Dual analysis indicates that the decreased anti-BrdUrd staining is largely restricted to cells in the early S p...Continue Reading

Citations

Oct 1, 2002·Acta Neuropsychiatrica·Marta KuberaMichael Maes
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