title: Altered growth hormone (GH) secretion in vivo and in vitro in the diabetes-prone BB/Worcester rat.
abstract: Diminished concentrations of growth hormone (GH) have been observed in the male BB/Wor rat with diabetes mellitus (DM). The precise mechanism(s) responsible for the altered GH levels is not entirely understood. We have therefore employed independent techniques to investigate potential alterations in: 1) the peripheral metabolism of the hormone; 2) GH release by somatotropes; and 3) hypothalamic regulation of GH secretion. An extra group of insulin-untreated animals was included for the studies of acute DM. The results demonstrate diminished circulating mean concentrations of GH (35 +/- 4 vs. 16 +/- 4 micrograms/l; mean +/- SEM; control vs. animal with DM; P = 0.006) due to impaired GH secretion. In particular, there was a decrease in the mass of GH secreted per burst (230 +/- 22 vs. 136 +/- 34 micrograms/l; P = 0.04) and in the GH secretory rate (24 +/- 4 vs. 9 +/- 3 micrograms/l/min; P < 0.01). No differences in the secretory burst frequency, (5.3 +/- 0.3 vs. 5.2 +/- 0.5 #/8-h; P = 0.68), secretory half-duration (10 +/- 2 vs. 17 +/- 2 min; P = 0.09), or serum GH half-life (8 +/- 1 vs. 6 +/- 1 min; P = 0.13) were observed. In vitro studies of acutely dispersed somatotropes obtained from rats with DM demonstrated increased sensitivity to GHRH (1 nM), as detected by a greater mean hemolytic plaque area following exposure to an EC50 dose of the secretagogue (14.3 +/- 3.3 vs. 17.4 +/- 3.5 microns 2 x 10(3); P = 0.049), and diminished sensitivity to SRIH (1 nM) inhibition of GH release following exposure to an EC50 dose of the secretagogue (10.0 +/- 1.2 vs. 14.9 +/- 2.3 microns2 x 10(3); P = 0.026). The number of the pituitary cells (18.0 +/- 2.8 vs. 15.3 +/- 1.0 x 10(5) cells; P = 0.38) as well as the number of somatotropes (7.3 +/- 1.4 vs. 7.6 +/- 0.9 x 10(5) cells; P = 0.87) were indistinguishable between experimental groups. Hypothalamic gene transcript levels for GH-releasing hormone (GHRH) and somatotropin release-inhibiting hormone (SRIH) were evaluated by in situ hybridization histochemistry to assess cellular synthetic activity.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: F
authors.initials: F
authors.lastname: Nieves-Rivera
authors.forename: J R
authors.initials: JR
authors.lastname: Kerrigan
authors.forename: R J
authors.initials: RJ
authors.lastname: Krieg
authors.forename: J
authors.initials: J
authors.lastname: Egan
authors.forename: L J
authors.initials: LJ
authors.lastname: Hwang
authors.forename: E
authors.initials: E
authors.lastname: Truumees
authors.forename: J D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: W S
authors.initials: WS
authors.lastname: Evans
authors.forename: A D
authors.initials: AD
authors.lastname: Rogol
mesh_terms: D000367:Age Factors; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D013004:Somatostatin / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D013004:Somatostatin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone