Effects of insulin on rat anterior pituitary cells. Inhibition of growth hormone secretion and mRNA levels.
We recently reported that insulin inhibits basal and cortisone- and T3-stimulated GH secretion by GH3 rat pituitary tumor cells. The effects of purified semisynthetic human insulin were therefore tested on long-term GH secretion in normal pituitary cells. Primary monolayer cultures derived from male rat pituitaries were grown in serum-free defined medium. Insulin (7 nM) maximally inhibited basal GH secretion by almost 60% after 72 h, with 50% of maximal GH suppression occurring with 1.75 nM insulin. Insulin receptor antiserum blocked the suppression of GH by 7 nM insulin, but had no effect on the suppression of GH by IGF-I (3.25 nM). GRF (100 pM) stimulated GH two- to threefold during 48 h. Insulin (7 nM) prevented the stimulation of GH induced by up to 1 nM GRF (P less than 0.01) and this suppression was also selectively blocked by insulin receptor antiserum. The inhibition of GRF-stimulated GH required a lag period of 48 h and the dose of insulin required for 50% inhibition of GRF stimulation was 3.5 nM. Insulin did not alter the degradation rate of 125I-GH in these cultures and medium glucose concentrations were not different in control or insulin-treated wells for up to 72 h of incubation. The insulin-induced suppression of GH was also observed when cells were grown in glucose-free medium. Insulin did not nonselectively suppress cell secretion, as PRL secretion was mildly stimulated (P less than 0.01) by insulin in the same cultures. Fibroblast growth factor, epidermal growth factor, and insulin A-chain at similar doses did not alter basal or GRF-stimulated GH secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamashita
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D000818:Animals; D004305:Dose-Response Relationship, Drug; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009693:Nucleic Acid Hybridization; D010903:Pituitary Gland, Anterior / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D012333:RNA, Messenger; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone