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Suppression of episodic growth hormone secretion in streptozotocin-induced diabetic mice: time-course studies on the hypothalamic pituitary axis.

Abstract：

:To elucidate the roles of the hypothalamic peptides, GH-releasing hormone (GRH) and somatostatin (SRIH), potentially responsible for altered GH dynamics in diabetes, we studied the time courses of their changes in level associated with altered GH secretion in streptozotocin (STZ)-induced diabetic mice. Diabetic mice were used at 4, 7, and 14 days after STZ injection for analyses of 1) GH secretion in vivo, 2) hypothalamic GRH and SRIH messenger RNA (mRNA) levels, 3) pituitary GH mRNA and protein contents, and 4) pituitary GH response to GRH in vitro. GH secretion was completely suppressed 7 and 14 days after STZ injection. The hypothalamic GRH mRNA level was reduced to 59.8%, 61.2%, and 48.5% of control values at 4, 7, and 14 days, respectively. In contrast, the hypothalamic SRIH mRNA level was not altered at all of these time points. Pituitary GH mRNA and protein contents were significantly reduced to 70.2% and 61.5% of those in controls, respectively, only at 14 days. Pituitary GH responses to GRH at three doses (10, 50, and 250 nM) in vitro were remarkably increased at 4, 7, and 14 days. These findings indicate that the diabetic state rapidly and primarily inhibits hypothalamic GRH gene expression without affecting SRIH. A persistent decrease in hypothalamic GRH tone has been suggested to result in inhibition of GH synthesis in the pituitary. Enhancement of GH responsiveness to GRH may be due to the up-regulation of GRH receptors in the pituitary.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Murao S,Sato M,Tamaki M,Niimi M,Ishida T,Takahara J

doi

10.1210/endo.136.10.7664670

subject

Has Abstract

pub_date

1995-10-01 00:00:00

pages

4498-504

issue

10

eissn

0013-7227

issn

1945-7170

journal_volume

136

pub_type

杂志文章

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