Differential effects of thyrotropin-releasing hormone, vasoactive intestinal peptide, phorbol ester, and depolarization in GH4C1 rat pituitary cells. 1985

T Aizawa, and P M Hinkle

The sequence of PRL and GH release from GH4C1 cells was studied in perifusion and static culture systems. The secretory pattern elicited by TRH differed from those caused by depolarizing concentrations of KCl (Ca2+-initiated secretion), vasoactive intestinal peptide (VIP), 8-bromo-cAMP, and forskolin (cAMP-mediated secretion), and 12-O-tetradecanoylphorbol-13-acetate (TPA) (protein kinase C activation). TRH, K+, VIP, and TPA all caused secretion within 1 min in the perifusion system but the peak response to TRH and depolarization occurred earlier than the peak responses to TPA and VIP. PRL and GH release in response to a pulsatile application of TRH (0.4-min pulse every 5 min for 25 min) did not decline with a low dose, indicating that acute desensitization does not occur, but did decrease with a high concentration. When cells in the perifusion system were subjected to continuous stimulation, TRH caused a biphasic response with a 2- to 3-min period of high secretion followed by a second phase in which GH and PRL secretion were 60-70% the rates in the first phase. KCl caused predominantly first-phase secretion, and TPA caused a biphasic secretory pattern with a delay in its peak of action. VIP caused a modest but prolonged response whether administered in a pulsatile or sustained manner. When GH-cells were exposed to 100 nM TRH for 2 days, [3H] [N3-methyl-His2]TRH binding was decreased (down-regulation), intracellular PRL was increased (170% of control), and intracellular GH was decreased (65% of control). In these down-regulated cells, baseline PRL and GH secretion were changed in proportion to the relative intracellular hormone content. The responsiveness to TRH, KCl, and TPA during the initial 10-min period (first phase) was reduced; however, the responsiveness to these substances in the subsequent 50-min period (second phase) was unchanged. The ED50 for TRH stimulation of hormone release was increased 2- to 4-fold in down-regulated cells, but the dose-response curves for other secretagogues were not shifted. These data suggest that the initial burst of hormone release caused by TRH is mediated by Ca2+, and that prolonged exposure to TRH causes homologous desensitization.

UI MeSH Term Description Entries
D010704 Phorbols The parent alcohol of the tumor promoting compounds from CROTON OIL (Croton tiglium). Tigliane,Tiglianes
D010902 Pituitary Gland A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM. Hypophysis,Hypothalamus, Infundibular,Infundibular Stalk,Infundibular Stem,Infundibulum (Hypophysis),Infundibulum, Hypophyseal,Pituitary Stalk,Hypophyseal Infundibulum,Hypophyseal Stalk,Hypophysis Cerebri,Infundibulum,Cerebri, Hypophysis,Cerebrus, Hypophysis,Gland, Pituitary,Glands, Pituitary,Hypophyseal Stalks,Hypophyses,Hypophysis Cerebrus,Infundibular Hypothalamus,Infundibular Stalks,Infundibulums,Pituitary Glands,Pituitary Stalks,Stalk, Hypophyseal,Stalk, Infundibular,Stalks, Hypophyseal,Stalks, Infundibular
D011189 Potassium Chloride A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA. Slow-K,Chloride, Potassium
D011388 Prolactin A lactogenic hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). It is a polypeptide of approximately 23 kD. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Prolactin receptors are present in the mammary gland, hypothalamus, liver, ovary, testis, and prostate. Lactogenic Hormone, Pituitary,Mammotropic Hormone, Pituitary,Mammotropin,PRL (Prolactin),Hormone, Pituitary Lactogenic,Hormone, Pituitary Mammotropic,Pituitary Lactogenic Hormone,Pituitary Mammotropic Hormone
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D004357 Drug Synergism The action of a drug in promoting or enhancing the effectiveness of another drug. Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D004563 Electrochemistry The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes. Electrochemistries
D005576 Colforsin Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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