Regulation of sexually dimorphic hepatic steroid metabolism by the somatostatin-growth hormone axis.

Lesions in the periventricular hypothalamic area in male rats results in a "feminization" of steroid metabolizing enzymes in the liver. These lesions also resulted in a decrease of somatostatin levels in the median eminence. Since blockade of somatostatin by in vivo administration of an antiserum also caused "feminization" of the liver, it is possible that at least one hypothalmic factor responsible for "feminization" is related to somatostatin.

Relationship between the biological and immunological activities of growth hormone circulating in normal rats.

The ability of GH to induce refractoriness to its own insulin-like effect in adipose tissue is highly specific for GH. Moreover, refractoriness to the insulin-like action of GH can be induced with low concentrations of GH in the range of 10 ng/ml. In the present study, the ability of plasma from normal rats to induce refractoriness to the effect of GH on the production of 14CO2 from [14C]glucose in epididymal fat pads from hypophysectomized rats was examined as a measure of a GH-specific biological effect of the plasma.

A hybrid noncovalent complex of fragments of porcine and human growth hormones with diabetogenic activity.

Although porcine GH (pGH) and human GH (hGH) are structurally related, their structures differ to the extent that, unlike hGH, pGH is not active in primates and does not exhibit lactogenic activity. Therefore, it was of interest to determine whether hybrid noncovalent complexes could be formed by complementation of large fragments of pGH with fragments of hGH and to study the immunological and biological properties of such hybrids. For this purpose, pGH was digested with bovine thrombin conjugated to Sepharose.

Effects of in vivo administration of antiserum to rat growth hormone on body growth and insulin responsiveness in adipose tissue.

To explore the short term effects of endogenous GH on body growth, glucose metabolism, and insulin responsiveness in adipose tissue, 35- to 40-day-old male rats were treated with a potent goat antiserum against rat GH (ArGHS). The administration of ArGHS, but not normal goat serum, caused a dose-dependent decrease in body weight gain and longitudinal bone growth, as measured by the tetracycline method. Glucose metabolism was measured by determining the production of CO2 from [14C]glucose in epididymal fat pad.

Specific binding of growth hormone to isolated chondrocytes from rabbit ear and epiphyseal plate.

Chondrocytes were isolated from rabbit ear, epiphyseal and rib cartilage, and their ability to bind 125I-labeled human growth hormone (hGH) was investigated. The total binding of hormone to ear chondrocytes increased with time until 4-6 h, whereas non-specific binding did not increase. Total binding was 1-3% of total counts added, and non-specific binding was 10-20% of total binding.

Sites of action of testosterone and estradiol on longitudinal bone growth.

In this study the mechanisms by which sex steroids influence body growth were investigated. The effect of different doses of testosterone propionate on longitudinal bone growth and body weight gain was studied in a) gonadectomized male rats, b) gonadohypophysectomized male rats, and c) gonadohypophysectomized male rats given replacement therapy with bovine growth hormone (bGH). The effect of different doses of estradiol benzoate on the same growth parameters was studied in female rats divided into the same experimental groups as the males.

Ability of growth hormone fragments to complete with 125I-iodinated human growth hormone for specific binding to isolated adipocytes of hypophysectomized rats.

Several noncovalent complexes of large fragments of human GH, which are less active than native human GH in stimulating glucose metabolism in adipose tissue of hypophysectomized rats, were tested for their ability to compete with 125I-iodinated human GH for specific binding to isolated adipocytes of hypophysectomized rats. The complexes tested were A (residues 1-134 + residues 141-191; S-carbamidomethylated), B (residues 1-134 + residues 135-191; S-carbamidomethylated) and C (residues 1-134 + residues 135-191; S-carboxymethylated). When compared to native human GH, the complexes were less active in competing with 125I-iodinated human GH for specific binding to adipocytes, and their order of potency in the binding assay (A greater than B greater than C) was similar to that of their respective activities in stimulating glucose metabolism in isolated adipose tissue of hypophysectomized rats.

Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats.

The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats. Replacement therapy with 3 different doses of human GH [(hGH) Crescormone] was started 10-14 days after hypophysectomy and was continued for 5 days. Longitudinal bone growth, as measured by the tetracycline method, and body weight were determined during the injection period.

Circumstantial evidence for a role of the secretory pattern of growth hormone in control of body growth.

The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats which were given replacement therapy with corticosteroids, thyroxine and GH with start of therapy on the day of surgery. Longitudinal bone growth, as determined by the tetracycline method, was measured during the last 5 days of the 9 day long period with replacement therapy. The daily replacement dose of GH (bGH-17:NIH) was 200 micrograms and was given on 1, 2, 4 or 8 occasions.

Effects of gonadectomy and testosterone replacement on growth hormone response to alpha 2 adrenergic stimulation in the male rat.

The growth hormone (GH) response to clonidine in reserpine-pretreated rats is a putative in vivo model to reflect activation of central postsynaptic alpha 2 receptors. In the present study the influence of testosterone on the responsiveness of central alpha 2 receptors was investigated using this method. One week after operation the GH response to clonidine was drastically reduced in gonadectomized adult male rats compared to sham-operated controls.

Up- and down- regulation of central postsynaptic alpha 2 receptors reflected in the growth hormone response to clonidine in reserpine-pretreated rats.

The alpha-adrenergic mechanisms exert a stimulatory influence on the secretion of growth hormone (GH) in the rat. In the present study the alpha receptors involved in GH regulation were characterized with respect to subtype. It was also investigated whether the GH response to alpha receptor agonists can be utilized to assess change in the responsiveness of central alpha receptors.

Effects of hypophysectomy, adrenalectomy and (-)-propranolol on ethanol-induced decrease in plasma amino acids.

In previous studies we have demonstrated that an acute dose of ethanol cause an immediate decrease in most plasma amino acids in both man and rat. This effect of ethanol is partly inhibited by the beta-adrenergic antagonist (-)-propranolol, partly by adrenalectomy or hypophysectomy and almost completely by a combination of adrenalectomy with (-)-propranolol. This finding suggests an involvement of both beta-adrenergic mechanisms and steroids from the adrenal cortex in the ethanol-induced decrease in plasma amino acids.

Importance of norepinephrine alpha 2-receptor activation for morphine-induced rat growth hormone secretion.

The normal pulsatile secretion of rat growth hormone (rGH) requires intact function in monoaminergic neurons. The importance of norepinephrine (NE) for the secretion is well documented, while the roles of dopamine (DA) and 5-hydroxytryptamine (5-HT) are still a matter of controversy. Morphine, as well as endogenous opioid peptides, are known to stimulate the secretion of GH.

Evidence for a growth hormone releasing factor mediating alpha-adrenergic influence on growth hormone secretion in the rat.

The effects of adrenergic receptor agonists on GH secretion were studied in adult, male rats pretreated with reserpine and somatostatin antiserum. Frequent blood samples were obtained from intra-aortic cannulae. Plasma GH was determined by radioimmunoassay.

Enhanced growth hormone response to clonidine in the spontaneously hypertensive rat.

Plasma concentrations of growth hormone (GH) were measured after administration of clonidine (0.5 mg/kg) to spontaneously hypertensive (SH) rats and normotensive Wistar Kyoto controls. All rats were pretreated with reserpine (10 mg/kg).

Monoaminergic control of episodic growth hormone secretion in the rat: effects of reserpine, alpha-methyl-p-tyrosine, p-chlorophenylalanine, and haloperidol.

The effects on GH secretion of reserpine, alpha-methyl-p-tyrosine (alpha-MT), p-chlorophenylalanine (PCPA), and haloperidol were studied in undisturbed, unanesthetized male rats with implanted intraaortic cannulae. The effects of the various drug treatments on motor activity and brain levels of catecholamines (CAs) and 5-hydroxytryptamine (5-HT) as well as the synthesis of the biogenic amines were also studied. Reserpine (10 mg/kg, ip) completely inhibited GH secretion for at least 15 h.

In vitro effects of growth hormone on protein synthesis and amino acid transport in the rat diaphragm after acute hypophysectomy.

The effects of growth hormone (GH) in vitro on phenylalanine-14C incorporation to assess protein synthesis and on alpha-aminoisobutyric-1-3H accumulation to measure amino acid transport in the diaphragm muscle of the rat were investigated 2, 6 and 24 h after hypophysectomy or sham-operation. In hypophysectomized animals protein synthesis was depressed. GH in vitro was without effect 2 h after hypophysectomy but stimulated protein synthesis 6 and 24 h after the operation.