下垂体細胞単層培養法を用いたラット及びヒト成長ホルモン、プロラクチン分泌機序に関する研究 : とくに下垂体レベルにおけるDopamineの役割について
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概要
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Using rat anterior pituitary monolayer cell culture system, the regulating mechanism of rat growth hormone (rGH) and prolactin (rPRL) secretion was studied in vitro-mainly about the dopaminergic regulation at the pituitary level. As a preliminary study, the effect of substances with known direct action on the pituitary, i.e., prostaglandin E_1 (PGE_1) , rat hypothalamic extract (HE) and thyrotropin releasing hormone (TRH) on this system was tested, followed by studies on the dopaminergic regulating mechanism of PRL secretion, including the action of dopamine and L-Dopa and the interactions between dopamine and anti-dopaminergic agents and bioactive brain peptides. The monolayer culture system was also applied to human pituitary cells from several acromegalic patients and autopsy cases for supplemental studies. The following results were obtained. 1. PGE_1 had direct GH stimulating effect from rat anterior pituitary cells dose dependently, but had failed to augment PRL release. Rat HE, 0.5〜3 median eminence equivalent/dish, apparently suppressed GH release. Synthetic TRH, 3×10^<-11>M〜3×10^<-7>M, significantly stimulated rat PRL release but only 3×10^<-10>M TRH was effective on GH release. 2. PRL release from rat pituitary was suppressed in a do.se dependent manner by 5×10^<-9>M〜5×10^<-7>M dopamine, but GH release was not affected by dopamine. L-Dopa, a precursor of dopamine, probably has to be converted to dopamine to inhibit PRL release, in view of the absence of such action in vitro. 3. The anti-dopaminergic agents, haloperidol, sulpiride, metoclopramide and YAU-125 had no stimulating effect on PRL release by themselves when added alone into the incubation medium, but antagonized dopaminergic PRL inhibition at the pituitary cells. 4. So-called opioid peptides-enkephalin and endorphin-apparently had no effect on PRL secretion at the pituitary level. 5. Neurotensin, substance-P and vasoactive intestinal polypeptide (VIP) antagonized the dopaminergic PRL inhibiting action on the pituitary, although none of them had direct stimulating effect of PRL release by themselves in vitro. 6. In the human pituitary cell culture system, effect of dopamine on GH release was demonstrated on neither the pituitary adenoma cells derived from a patient with acromegaly nor normal pituitary cells obtained by autopsy. PRL secretion from normal human pituitary cells Was significantly suppressed by dopamine. The paradoxical increase of GH release was demonstrated from cells from a patient with acromegaly, suggesting a parallelism between phenomena in vivo and in vitro. The monolayer cell culture system of the pituitary thus appears to be quite useful in the studies on the mechanism of GH and PRL secretion at the pituitary level.
- 神戸大学の論文