Basal Serum Growth Hormone Concentrations Research Articles

Reduced levels of growth hormone, insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

OBJECTIVEChildren with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone,...

Metabolic changes during the transition from the fed to the acute feed-deprived state in prepuberal and mature gilts.

The present study compared the metabolic response to acute feed deprivation in ovariectomized prepuberal (P; n = 6), 62 +/- 2 kg BW, and mature (M; n = 6) gilts, 124 +/- 4 kg BW. Blood was collected at 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 28, 32, 40, and 48 h after initiation of feeding. Samples were quantified for glucose, insulin, free fatty acids (FFA), beta-hydroxybutyrate (HBA), IGF-I, IGF binding proteins (BP)-1 to -4, cortisol, and amino acids (AA). At 24 h, blood samples were collected every 15 min for 8 h and an additional 1 h after i.v. injection of GnRH (.2 microgram/kg BW) and growth hormone-releasing factor (GRF; 1 microgram/kg BW). Samples were assayed for growth hormone (GH) and LH. Serum insulin concentrations were lower (P < .05) in P gilts. Plasma glucose concentrations were similar. Serum FFA concentrations were greater (P < .05) in P gilts. Serum concentrations of HBA were greater (P < .001) in P gilts at 48 h. Serum IGF-I concentrations were lower (P < .05) in P gilts by 16 h. Serum IGFBP-1-4 levels were similar. Serum cortisol concentrations were similar. Serum concentrations of the essential AA, isoleucine, lysine, threonine, valine, and phenylalanine were greater (P < .05) in P gilts at 40 h. Serum LH concentrations and response to GnRH were similar. Basal serum GH concentrations and peak response to GRF were greater (P < .05) in P than in M gilts. The transition from fed to unfed state occurs more rapidly in P than in M gilts.

Acromegaly in 14 Cats

Acromegaly was diagnosed in 14 middle-aged to old cats of mixed breeding. Thirteen (93%) of the cats were male and one was female. The earliest clinical signs in the 14 cats included polyuria, polydipsia, polyphagia, all of which were associated with untreated diabetes mellitus. All developed severe insulin resistance within a few months; peak insulin dosages required to control severe hyperglycemia ranged from 20 to 130 U per day. Other clinical findings weeks to months after diagnosis included enlargement of one or more organs (e.g., liver, heart, kidneys, and tongue) (n = 14), cardiomyopathy (n = 13), increase in body size and weight gain (n = 8), nephropathy associated with azotemia and clinical signs of renal failure (n = 7), degenerative arthropathy (n = 6), and central nervous system signs (i.e., circling and seizures) caused by enlargement of the pituitary tumor (n = 2). The diagnosis of acromegaly was confirmed by demonstration of extremely high basal serum growth hormone concentrations (22 to 131 micrograms/l) in all cats. Computerized tomography disclosed a mass in the region of the pituitary gland and hypothalamus in five of the six cats in which it was performed. Two cats were treated by cobalt radiotherapy followed by administration of a somatostatin analogue (octreotide), whereas two cats were treated with octreotide alone. Treatment had little to no effect in decreasing serum GH concentrations in any of the cats. Eleven of the 14 cats were euthanized or died four to 42 months (median survival time, 20.5 months) after the onset of acromegaly because of renal failure (n = 2), congestive heart failure (n = 1), concomitant renal failure and congestive heart failure (n = 3), progressive neurologic signs (n = 2), persistent anorexia and lethargy of unknown cause (n = 1), the owner's unwillingness to treat the diabetes mellitus (n = 1), or unknown causes (n = 1). Results of necropsy examination in ten cats revealed a large pituitary acidophil adenoma (n = 10), marked left ventricular and septal hypertrophy (n = 7), dilated cardiomyopathy (n = 1), arthropathy affecting the shoulder, elbow, or stifle (n = 5), and glomerulopathy characterized by expansion of the mesangial matrix and variable periglomerular fibrosis (n = 10).

Dynamic of the GRF-induced GH response in genetically obese Zucker rats: influence of central and peripheral factors

To determine the time onset of the growth hormone (GH) alteration in the genetically obese rat, we studied the in vivo and in vitro rat growth hormone releasing factor (rGRF(1–29)NH 2)-induced GH secretion in 6- and 8-week-old lean and obese male Zucker rats. Under sodium pentobarbital anesthesia, rGRF(1–29)NH 2 (GRF) was injected intravenously at two doses: 0.8 and 4.0 μg/kg b.w. Basal serum GH concentrations were similar in lean and obese age-matched animals. The GH response to both GRF doses tested was unchanged in 6-week-old obese rats as compared to their lean litter mates. In contrast, a significant decrease of the GH secretion in response to 4.0 μg/kg b.w. GRF was observed in the 8-week-old obese rats. The effect of GRF (1.56, 6.25 and 12.5 pM) was further studied in vitro, in a perifusion system of freshly dispersed anterior pituitary cells of lean and obese Zucker rats. Basal GH release was similar in the 6-week-old animal group. In contrast, it was significantly decreased in 8-week-old obese rats as compared to their lean litter mates. Stimulated GH response to 1.56 and 6.25 pM GRF was significantly greater in the 6-week-old obese group than in the age-matched control group. In contrast, the GH response to all GRF concentrations tested was significantly decreased in the 8-week-old obese rats as compared to their respective lean siblings. In 8-week-old obese rats, a decrease of GH pituitary content and an increase of hypothalamic somatostatin (SRIF) concentration were observed. Insulin and free fatty acid serum were significantly increased in 8-week-old obese rats. In contrast, lower insulin-like growth factor I serum levels were observed in the obese animals as compared to their lean litter mates. Finally, to further clarify the role of the periphery in the inhibiton of GH secretion observed in the 8-week-old fatty rats, we exposed cultured pituitary cells of 8-week-old lean animals to 17% serum of their obese litter mates. A significant decrease of GRF-stimulated GH secretion of lean rat pituitary cells exposed to the obese serum was noted ( P < 0.05). This study demonstrates that, in the obese Zucker rat, an alteration of the GH response to GRF is evident by the 8th week of life. This defective GH secretion could be related to peripheral and central abnormalities.

In vitro and in vivo Growth Hormone Responsiveness to Growth Hormone-Releasing Factor in Male and Female Zucker Rats

In order to determine whether there is an anomaly in the pituitary responsiveness to growth hormone (GH)-releasing factor in the genetically obese rat, we examined the in vitro and in vivo effects of rGRF(1-29)NH2 (GRF) on GH release in male and female Zucker rats. The effect of increasing GRF concentrations (1.56, 6.25, 12.5 25 and 50 pM) was first tested on GH release from freshly perifused anterior pituitary cells. In both sexes, the GH response per one pituitary equivalent to each GRF concentration tested was reduced in the obese group. However, when GH release was expressed as a percent of initial cell GH content, there was no difference between the lean and the obese groups. Furthermore, under pentobarbital anesthesia, GRF was injected intravenously at two consecutive doses of 0.8 and 4.0 microgram/kg body weight in obese and lean animals. In both sexes, the GH response to each dose of GRF tested was decreased in the obese group. Basal serum GH concentrations were similar in male and female obese rats compared to their respective lean siblings. In conclusion, this study demonstrates a decrease of the in vitro and in vivo pituitary response to GRF in the obese Zucker rat, suggesting a possible secondary defect at the pituitary level.

Growth hormone responsiveness in vivo and in vitro to growth hormone releasing factor in the spontaneously diabetic BB Wistar rat.

In order to determine whether there is an abnormality in the pituitary responsiveness to GRF in the diabetic rat, we examined the in vivo and in vitro effects of hGRF-44 NH2 (hGRF) on growth hormone (GH) release in the spontaneously diabetic BB Wistar rat. Under pentobarbital anesthesia, hGRF was injected intravenously at a dose of 500 ng/kg in male diabetic BB Wistar rats (n = 11) and in male control Wistar rats matched for weight (n = 11). Basal serum GH concentrations were significantly lower in the diabetic group, (123 +/- 5 ng/ml, mean +/- SEM) than in the control group (362 +/- 15 ng/ml). However, the GH response to hGRF was significantly greater in the diabetic group (GH increment 873 +/- 153 ng/ml) than in the control group (268 +/- 91 ng/ml). The effect of hGRF was further tested in a perifusion system of freshly dispersed anterior pituitary cells of diabetic BB Wistar rats and control Wistar rats. Basal secretion rate of GH from cells of diabetic rats (0.85 +/- 0.06 microgram/2 pituitaries X 2 min) was lower than that from cells of control rats (1.60 +/- 0.18 micrograms/2 pituitaries X 2 min). The GH response to 2-min pulses of hGRF at concentrations of 1.56, 6.25, and 25 pM with and without somatostatin 10(-9) M was significantly greater in the diabetic group than in the control group. In conclusion, there is in the spontaneously diabetic rat an increased in vivo and in vitro GH responsiveness to exogenous hGRF suggesting an abnormality of GH regulation at the pituitary level.

Effect of Clozapine on Apomorphine-Induced Growth Hormone Secretion and Serum Prolactin Concentrations in Schizophrenia

Clozapine had no effect on basal serum growth hormone concentrations in 10 schizophrenic patients but significantly inhibited the apomorphine-induced growth hormone increase that occurred in 7 subjects. Clozapine caused a slight (17%) but significant elevation in basal serum prolactin levels. These data suggest that in man clozapine, like other neuroleptics, blocks dopamine receptors, at least in the hypothalamic-pituitary axis.