Conversion of bovine growth hormone cysteine residues to serine affects secretion by cultured cells and growth rates in transgenic mice.

Groups of underyearling coho salmon (Oncorhynchus kisutch) were acclimated to 10 C well water and a photoperiod of 12 h L:12 h D. Excess ration (Oregon Moist Pellet) was presented daily. Doses of bovine growth hormone (5, 10, 20, 30, or 90 μg bGH/g body wt) and L-thyroxine (0.5, 5, or 30 μg T4/g) were administered over a period of 84 days (phase I) either by injection (via dorsal musculature or peritoneal cavity) or by hormone cholesterol implants into the muscle. Administration frequency of bGH and T4 was such (range 2 times/wk-1 time/3 wk) that fish theoretically received either 10 or 30 μg bGH/g per wk or 1 or 10 μg T4/g per wk. Control fish received either alkaline saline (pH 9.5) or a cholesterol pellet. After cessation of treatment the fish were observed for an additional 84 days (phase II). During phase I, growth rates (weight) for bGH fish (2.0–2.4% per day) and for T4 fish (0.97–1.1% per day) were significantly higher than those of control fish (0.42–0.59% per day). Among bGH fish, dorsal musculature injection (2 times/wk) was significantly more effective than intraperitoneal injection (1 time/2 wk).Increases in weight above control for bGH fish at 84 days ranged from 220 to 369%. Those for T4 fish extended from 47 to 78%. In phase II, control fish growth rates were higher (0.61–0.67% per day) than those for bGH fish (0.47–0.57% per day) and T4 fish (0.32–0.44% per day). Administration of bGH and T4 (high dose) caused a progressive decline in condition factor of fish from the control range. This trend was stopped and reversed in phase II.At 84 days, generally no significant differences were detected among groups for percentages of muscle water. However, some groups had significantly higher (bGH) and others lower (T4) percentages of muscle protein relative to those of control fish. Also, significant increases (T4) and decreases (bGH) in muscle lipid percentages were found. Hormone treatment altered the histological structure of the ovary, thyroid, exocrine (T4) and endocrine (bGH) pancreas, and somatotrop cells (T4) of the pituitary. A poor growth response was noted for two groups of coho administered bGH after acclimation to sea water.

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Effects of bovine growth hormone (GH) expression in transgenic mice on serum and pituitary immunoreactive mouse GH levels and pituitary GH-releasing factor binding sites

Acta Endocrinologica ◽

10.1530/acta.0.1290446 ◽

1993 ◽

Vol 129 (5) ◽

pp. 446-452 ◽

Cited By ~ 18

Author(s):

AI Sotelo ◽

A Bartke ◽

D Turyn

Keyword(s):

Growth Hormone ◽

Transgenic Mice ◽

Binding Sites ◽

Phosphoenolpyruvate Carboxykinase ◽

Serum Levels ◽

Bovine Growth Hormone ◽

Complete Suppression ◽

Over Expression ◽

Pituitary Glands ◽

Scatchard Plots

Pituitary and serum levels of homologous growth hormone (GH) and characteristics of specific GH-releasing factor (GHRF) binding to pituitary homogenates were examined in transgenic mice expressing bovine GH (bGH) gene regulated by different promoters [mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase (PEPCK)] and in their normal littermates. Pituitary GH concentration and GHRF binding were reduced by approximately 50% in transgenic MT-bGH mice in which serum bGH levels were about 20 μg/l and by approximately 95% in transgenic PEPCK-bGH mice in which serum bGH levels were tenfold higher. Suppression of plasma immunoreactive mouse GH (mGH) levels was detected in MT-bGH but not in PEPCK-bGH animals, presumably due to cross-reaction of the antiserum employed with bGH. Scatchard plots of GHRF binding to washed homogenates of pituitary glands from normal and young adult MT-bGH transgenic mice were curvilinear, indicating the presence of two types of binding sites, with low and high affinities. Both types of binding sites were reduced in number in MT-bGH transgenic mice without changes in their affinity. In 5–7-month-old MT-bGH transgenic mice there were changes in pituitary GH levels, in GHRF binding levels and in characteristics of GHRF binding that closely resembled the alterations described previously in aging rats. We conclude that over-expression of heterologous GH genes in transgenic mice can lead to partial or virtually complete suppression of somatotroph function, depending on the levels of heterologous GH in the circulation, and that transgenic MT-bGH mice exhibit symptoms of remarkably early onset of neuroendocrine aging.

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