Defective thyroliberin-induced prolactin synthesis and release in a hybrid GH strain.
The hybrid GH cell strain, 928-9b, isolated from PRL+ (prolactin [PRL] producing) GH4Cl and PRL (PRL non-producing) F1BGH(1)2C1 cells, has specific TRH (thyroliberin) receptors, yet does not respond to this peptide hormone. Unlike the parent strain, GH4C1, TRH does not stimulate synthesis or release of PRL in the hybrid strain. In contrast, treatment of 928-9b cells with another peptide, EGF (epidermal growth factor), stimulates both release and synthesis of PRL. The number of EGF receptors in the hybrid strain (2.5 x 10(3)/cell) and the affinity of these receptors for ligand (2.2 nM) are comparable to that of the parent strain, GH4C1. The EGF dose response curve is also essentially the same for parent and hybrid cells for the enhancement of PRL production. A 3-8-fold enhancement of PRL production is observed and 1/2 maximal enhancement occurs at approximately 5 x 10(-11) M EGF for both strains. TRH does not have any potentiating effect on EGF-induced stimulation of PRL release or PRL synthesis in the hybrid strain. Although EGF and TRH have similar biological effects in responsive GH cells, binding of one hormone to its receptors does not modulate the binding of the heterologous hormone. These findings demonstrate that more than one effect of TRH is defective in 928-9b cells even though EGF responses are intact. This suggests that 1) TRH-stimulated PRL release and TRH-stimulated PRL production have a common intermediate step, and 2) TRH and EGF have a different mechanism of action in GH cells.
D000818:Animals; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors; D006822:Hybrid Cells / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D004815:Epidermal Growth Factor; D011388:Prolactin; D066246:ErbB Receptors