Pituitary hormone gene expression and secretion in human growth hormone-releasing hormone transgenic mice: focus on lactotroph function.
The human GH-releasing hormone (hGHRH) transgenic mouse has a hyperplastic anterior pituitary gland that eventually develops into an adenoma. We showed previously that the number of lactotrophs in the male hGHRH transgenic mouse is increased 2-fold, yet there is no concomitant increase in plasma levels of PRL. To further elucidate underlying changes in lactotroph function in the hGHRH transgenic mouse, the objectives of this study were to 1) examine the relative differences in PRL gene expression in transgenic mice and their siblings, 2) quantify PRL secretion at the level of the individual cell, 3) determine whether tyrosine hydroxylase gene expression and/or activity are altered in the hypothalamus of transgenic mice, and 4) assess dopamine receptor gene expression and functional sensitivity in lactotrophs of transgenic mice. Total PRL messenger RNA (mRNA) levels were increased nearly 5-fold in the hGHRH transgenic mouse, whereas the concentrations of PRL mRNA (PRL mRNA per microg total RNA) were unchanged. In contrast, total PRL contents were unchanged, whereas the concentrations of PRL (micrograms of PRL per mg total protein) were decreased 3-fold. Hypothalamic tyrosine hydroxylase steady state mRNA levels were not altered in the hGHRH transgenic mice, but hypothalamic tyrosine hydroxylase activity was increased 2-fold in transgenic mice. Dopamine D2 receptor mRNA concentrations in the anterior pituitary were increased 2.5-fold in hGHRH transgenic mice, and total pituitary D2 receptor mRNA levels were increased nearly 10-fold. Furthermore, the basal secretory capacity of lactotrophs from transgenic mice was increased significantly at the level of the single cell, and dopamine inhibited the secretion of PRL to a greater extent in hGHRH transgenic mice. Thus, although the total number of lactotrophs is increased 2-fold in hGHRH transgenic mice, the present data are consistent with the hypothesis that increased hypothalamic dopamine synthesis and release coupled with an increase in D2 dopamine receptor gene expression and functional sensitivity in the pituitary result in normal plasma levels of PRL.
Moore
J P
JP
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington 40536-0084, USA.
Cai
A
A
Hostettler
M E
ME
Arbogast
L A
LA
Voogt
J L
JL
Hyde
J F
JF
D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000494:pharmacology; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism; D015151:Immunoblotting; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D010907:Pituitary Hormones / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D011388:Prolactin / Q000096:biosynthesis; D011863:Radioimmunoassay; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis / Q000235:genetics
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D004791:Enzyme Inhibitors; D006834:Hydrazines; D010907:Pituitary Hormones; D017448:Receptors, Dopamine D2; D011388:Prolactin; D013007:Growth Hormone-Releasing Hormone; C004297:3-hydroxybenzylhydrazine; D014446:Tyrosine 3-Monooxygenase