Effect of Testosterone on Growth Hormone Secretion in Patients with Anorchia and Delayed Puberty
01 May 1970-The Journal of Clinical Endocrinology and Metabolism (The Endocrine Society)-Vol. 30, Iss: 5, pp 615-618
TL;DR: The normalization of growth hormone release after one injection of testosterone might be helpful to exclude isolated growth hormone deficiency in boys with delayed puberty and small stature who present a doubtful growth hormone response to hypoglycemia.
Abstract: The effect of testosterone on plasma growth hormone response to hypoglycemia was studied in 4 patients with anorchia, in a patient with delayed puberty, and in a patient with panhypopituitarism. Insulin tolerance tests were performed a) without testosterone therapy, b) 2 days after a single injection of testosterone, and c) in 3 patients after 2–3 months of full replacement therapy. Testosterone led to an increased release of growth hormone in all 4 patients with anorchia and in the boy with delayed puberty. This increase appeared 2 days after a single injection of testosterone; it became still higher after 2–3 months of full replacement therapy. In the patient with panhypopituitarism, no growth hormone response was observed. The normalization of growth hormone release after one injection of testosterone might be helpful to exclude isolated growth hormone deficiency in boys with delayed puberty and small stature who present a doubtful growth hormone response to hypoglycemia.
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TL;DR: The results indicate that sex and age have independent and interrelated effects on GH secretion, and an amplifying action of estradiol on the neuroendocrine regulation of pulsatile GH release is suggested.
Abstract: We undertook a study of the separate and combined effects of age and sex on the pulsatile pattern of GH secretion. The 24-h secretory profile of GH was generated by 20-min sampling in 10 young women (aged 18-33 yr), 10 young men (aged 18-33 yr), 8 postmenopausal women (aged greater than 55 yr), and 8 older men (aged greater than 55 yr). A computer-assisted pulse analysis program was used to assess both total GH secretion, as reflected in the 24-h integrated GH concentration (IGHC), and pulsatile secretion, as denoted by pulse frequency, duration, amplitude, and the fraction of GH secreted in pulses during the 24-h period (FGHP). IGHC was significantly greater in women than in men (P less than 0.025) and greater in the young than in the old (P less than 0.003). The mean pulse amplitude, duration, and FGHP were each greater in the young (P less than 0.006, P less than 0.03, and P less than 0.0001, respectively), but not significantly different between the sexes. The mean pulse frequency was not affected by sex or age. The serum concentration of free estradiol, but not free testosterone, correlated with IGHC (r = 0.46; P less than 0.005), pulse amplitude (r = 0.53; P less than 0.001), and FGHP (r = 0.59; P less than 0.0002). After correcting for the effects of estradiol, neither sex nor age influenced IGHC or mean pulse amplitude, while the effect of age on FGHP was reduced from 81% to 29%. Of the indices of GH secretion, FGHP had the strongest correlation (r = 0.43; P less than 0.006) with somatomedin-C. Somatomedin-C declined significantly with age in both sexes. Our results indicate that sex and age have independent and interrelated effects on GH secretion. These effects can be largely accounted for by corresponding variations in endogenous estradiol levels. These observations suggest an amplifying action of estradiol on the neuroendocrine regulation of pulsatile GH release.
926 citations
TL;DR: It may be justifiable initially to limit use of GH to certain elderly patients such as those suffering from catabolic illnesses, malnourishment, burns, cachexia, etc, but a great deal more research will be necessary to determine whether normalization of GH and IGF-I levels in healthy older persons will lead to improvements in their physical and psychological functional capacity and quality of life.
Abstract: In humans, both aging and GH deficiency are associated with reduced protein synthesis, decreased lean body and bone mass, and increased percent body fat. In healthy individuals, spontaneous and stimulated GH secretion, as well as circulating IGF-I and IGFBP-3 levels, are significantly decreased with advancing age. The extent to which these age-related changes in GH and IGF-I contribute to alterations in body composition and function remains to be elucidated. GH treatment of GH-deficient adults or old men with reduced IGF-I levels with exogenous GH increases plasma IGF-I, nitrogen retention, and lean body mass, decreases percent body fat, and exerts little effect on bone mineral density. Short-term adverse effects of GH therapy have been minimized by using low-dose regimens, but it is still uncertain whether long-term GH supplementation in adult life increases the risk of metabolic abnormalities or malignancy. Administration of GHRH, which has been shown to maintain the pattern of pulsatile GH secretion in old men, may represent another possible physiological approach to therapy. It may be justifiable initially to limit use of GH to certain elderly patients such as those suffering from catabolic illnesses, malnourishment, burns, cachexia, etc. A great deal more research will be necessary to determine whether normalization of GH and IGF-I levels in healthy older persons will lead to improvements in their physical and psychological functional capacity and quality of life.
921 citations
TL;DR: A feminization of the liver develops after continuous, but not intermittent, administration of GH to hypophysectomized rats, suggesting that high, infrequent GH pulses with low plasma GH levels in between promotes growth more effectively than an intermediate, rather constant level of plasma GH.
Abstract: THE CLASSICAL CONCEPT of neuroendocrine control of the pituitary as proposed by Harris stipulates that the endocrine functions of the anterior pituitary are controlled by hypothalamic releasing factors or release-inhibiting factors. It was postulated that these factors are present in hypothalamic neurons which project into the median eminence (ME) of the basal hypothalamus and end in contact with the hypothalamic-hypophyseal portal vessels (1). It has subsequently been shown that growth hormone (GH) secretion is regulated by both stimulatory and inhibitory factors of hypothalamic origin. Like other anterior pituitary hormones, GH is secreted episodically. In all mammalian species so far studied spontaneous episodes of GH secretion occur several times over a 24-h period (2–8). Particularly in the adult male rat there is a striking regularity in the GH pulses which occur at 3- to 4-h intervals and reach levels of several hundred ng/ml.
715 citations
TL;DR: The present critical review examines hormonal regulation of body composition in infancy, childhood, and puberty using gonadal sex steroids and GH/IGF-I as prime determinants of evolving body composition.
Abstract: Body composition exhibits marked variations across the early human lifetime. The precise physiological mechanisms that drive such developmental adaptations are difficult to establish. This clinical challenge reflects an array of potentially confounding factors, such as marked intersubject differences in tissue compartments; the incremental nature of longitudinal intrasubject variations in body composition; technical limitations in quantitating the unobserved mass of mineral, fat, water, and muscle ad seriatim; and the multifold contributions of genetic, dietary, environmental, hormonal, nutritional, and behavioral signals to physical and sexual maturation. From an endocrine perspective (reviewed here), gonadal sex steroids and GH/IGF-I constitute prime determinants of evolving body composition. The present critical review examines hormonal regulation of body composition in infancy, childhood, and puberty.
407 citations
TL;DR: There was a highly significant relation between blood GH peak level and pretreatment height velocity in the HS patients, and partial HS patients are accelerated by HGH and should be treated; but their average acceleration is below that of total HS patients.
Abstract: (1) Human growth hormone (HGH) has been given for one whole year or longer to 100 patients, aged 1·5 to 19 years, participating in the Medical Research Council Clinical Trial of HGH. Each patient was measured 3-monthly for a control year before treatment, and the majority for a control year after the first treatment year. All measurements were made by one anthropometrist. Radiographic measurements of widths of bone, muscle, and fat in calf and upper arm were made. Methods and standards for assessing the significance of a given height acceleration are presented. (2) The characteristics at diagnosis are given of 35 patients with isolated GH deficiency or hyposomatotrophism (HS), 18 with craniopharyngiomas and other CNS lesions, 3 with multiple trophic hormone deficiency, 18 with low birthweight short stature, 4 with hereditary smallness and/or delay in growth, 4 with psychosocial short stature, 1 with high resting HGH and low somatomedin, 6 with Turner9s syndrome, and 11 with other diagnoses. (3) 29 of the 35 HS patients were boys and 13 had an abnormally small penis and ill-developed scrotum. Only 2 were sibs. Parents averaged 40th centile for height. 4 children developed growth-suppressing antibodies, and had to cease treatment. The mean standard deviation score (SDS) for height at diagnosis was -4·7, range -2·6 to -7·3. Bone age SDS averaged -3·2, range -0·8 to -5·7. Skinfold SDS averaged +0·91. Limb muscle width SDS averaged about -3·0. GH peak in insulin hypoglycaemia averaged 4·7 ± 0·7 μU/ml, range 1 to 13. (4) A category of partial growth hormone deficiency is defined as patients with GH peaks of 7-20 μU/ml inclusive and height velocity SDS in the year before treatment between -1 and -2. Total HS patients have GH peaks of 1 to 6 μU/ml inclusive and height velocity SDS of (5) There was a highly significant relation (r = -0·64) between blood GH peak level and pretreatment height velocity in the HS patients. (6) The LBW patients were 10 boys and 7 girls; all the boys had normal genitalia. The average height SDS at diagnosis was -3·7; parents9 height centile averaged 50th, bone age SDS -1·8, skinfold SDS -0·9. GH peaks were all above 30
374 citations