The prolactin response to thyrotrophin-releasing hormone is intact in the human male castrate.
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Aged↗
Biomedical subjects
D LeRoith
Publications and source records attributed to D LeRoith.
The TSH response to TRH is exaggerated in primary testicular failure and normal in the male castrate.
Basal TSH levels and the TSH response to TRH have been evaluated in 26 males aged 20-48 years with primary testicular failure, and 6 males aged 58-69 years who had been orchidectomised for prostatic carcinoma. The patients with testicular failure were sequentially challenged at 30 min intervals with iv LRH (100 microgram), TRH (200 microgram) and the dopaminergic antagonist, metoclopramide (10 mg). The castrates received a bolus of LRH and TRH given together. The responses in the 2 patient groups were compared to a group of 28 healthy male controls aged 20-40 years, who received the sequential protocol and 8 elderly controls aged 65-79 years, who were given the LRH, TRH bolus. Mean +/- SD basal TSH levels were 3.0 +/- 1.2 muU/ml in primary testicular failure and significantly greater than both control and castrate groups. The peak TSH response to TRH was 18.4 +/- 7.4 muU/ml in testicular failure and significantly greater than in the young controls, where it was 11.5 +/- 5.0 muU/ml. The peak levels in the castrates and in the elderly controls were similar to the young male controls. Total T4 and T3, as well as FTI, primary testicular failure had a reduction in their T3 resin uptake. The normal TSH profile in the castrates indicates that a testicular factor produces the exaggerated responses in primary testicular failure.
Adult↗
Insulin in insects and annelids.
The fruitfly, Drosophila melanogaster, and the earthworm, Annelida oligocheta, were extracted with acid-ethanol by a classic method for recovering insulin from the pancreas. When each extract was filtered on a Sephadex G-50 column, a distinct peak of insulin immunoreactivity. The material in this peak had reactivity insulin (equivalent to 0.1 to 2 ng of insulin/g wet weight) was recovered in the region typical of insulin bioassay, measuring stimulation of glucose oxidation or lipogenesis by isolated rat adipocytes. The bioactivity was partially or largely neutralized by anti-insulin antibodies. In concordance with previous work showing the presence of material very similar to insulin in the blowfly and molluscs, we have confirmed the presence of insulin in insects and extended the observation to the earthworms. These findings suggest that insulin is more widespread in invertebrates than was previously thought. In a companion study (Proc. Natl. Acad. Sci. USA 77:6184-88, 1980), we have demonstrated material similar to insulin in unicellular organisms.
Adipose Tissue↗
Evolutionary origins of vertebrate hormones: material very similar to adrenocorticotropic hormone, beta-endorphin, and dynorphin in protozoa.
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Adrenocorticotropic Hormone↗
Exaggerated prolactin response to thyrotropin-releasing hormone and metoclopramide in primary testicular failure.
Twenty-eight severely oligospermic and azoospermic men aged 20 to 42 years were challenged with luteinizing hormone (LH)-releasing hormone (LHRH), thyrotrophin-releasing hormone (TRH), and the dopaminergic antagonist, metoclopramide, given at 30-minute intervals. According to basal gonadotropin levels, the patients were subdivided into three groups: those with severe testicular failure (basal LH > 20 mIU/ml and FSH > 14 mIU/ml); those with moderate testicular failure with predominant seminiferous tubule involvement (LH < 20 mIU/ml and FSH > 14 mIU/ml) and those with mild testicular failure (LH < 20 mIU/ml and FSH < 14 mIU/ml. With one exception, mean basal prolactin (PRL) levels were normal in all patients. In all three groups, however, there was an exaggerated PRL response to TRH, the response in severe and moderate testicular failure being greater than that in mild testicular failure. The response to metoclopramide was increased only in the first two groups, not in the group with mild testicular failure. When individual patients and control subjects were considered together, the peak PRL response to TRH correlated with both basal and peak gonadotropin responses to LHRH. However, the PRL responses did not correlate with 17 beta-estradiol, estrone, testosterone, or the estradiol-testosterone ratio. It is concluded that oligospermic and azoospermic subjects with the most severe testicular failure and the highest gonadotropin levels have the greatest PRL increases after TRH and metoclopramide, indicating that the PRL response is related to the degree of testicular failure.
Adult↗
Acid-induced gastric inhibitory polypeptide secretion in man.
This study has assessed the effect of oral or intraduodenal HCl, administered alone or in combination with glucose, on gastric inhibitory polypeptide (GIP) and insulin secretion. Eight young males were given the following three oral tests: 30 g glucose, 150 cc 0.1 N HCl and the glucose-acid combination. Another group of eight controls received intraduodenal infusions of 20 g glucose, 75 cc 0.1 N HCl and their combination. All tests were performed in a random fashion at weekly intervals. When given alone, HCl did not influence glucose or insulin levels. However, HCl did produce an increase in GIP. The GIP response to acid was less than that to glucose and was delayed. The peak insulin and GIP responses with the glucose and glucose/acid combinations were similar with both the oral and intraduodenal routes. There was, however, a potentiation of both the GIP and insulin responses when intraduodenal acid was given with glucose. This effect on GIP and insulin was not evident with the oral glucose/acid load. It is concluded that HCl by itself is capable of stimulating GIP secretion. Since there was only a potentiation of insulin and GIP secretion when large doses of HCl were given together with glucose via the intraduodenal route, the physiological relevance of acid-induced GIP secretion remains to be resolved.
Administration, Oral↗
Dissociation of pituitary glycoprotein response to releasing hormones in chronic renal failure.
The LH, FSH and TSH response to LRH and TRH has been evaluated in patients with chronic renal failure. Basal gonadotrophins were elevated in 3 out of 6 males; one of 4 pre-menopausal females had increased basal LH. Exaggerated LH responses to LRH were noted in 4 out of 6 males and one of 4 females; FSH reponses were increased in 3 of these males. One male and one female had attenuated LH and FSH responses to LRH. Both testosterone and oestradiol levels were reduced. In 5 out of 6 subjects tested both pre- and post-dialysis there was a greater LH and FSH response to LRH following dialysis. This suggests the presence of a dialysable toxin which is inhibiting the gonadotrophin response to LRH. Gonadotrophin levels remained elevated during 4 h of dialysis suggesting prolongation of the metabolic clearance rate. Despite low T3 levels, TSH response to TRH (200 microgram) was only elicited in 2 of 6 cases. However, all 3 responded to 500 microgram and 2 out of 3 to 1000 microgram TRH, the third showing an attenuated response. TSH levels also remained persistently elevated in the responders. Dialysis however, failed to improve the relative TSH non-responsiveness to TRH. In conclusion the data has shown that there is a dissociation in glycoprotein hormone responses to releasing hormones in ureamia. Whereas the gonadotrophs retain their responsiveness to LRH, the thyrotrophs appear to be more effected by the uraemic process and demonstrate an impaired response to TRH.
Adult↗
The effect of clomiphene citrate on pubertal gynaecomastia.
Clomiphene citrate 100 mg daily was used to treat 28 boys with pubertal gynaecomastia. Six failed to complete the course and of the remaining, 14 (64%) responded within 6 months of commencement of therapy. LH, FSH, testosterone and oestradiol levels rose during therapy. It is suggested that clomiphene affects gynaecomastia locally as an anti-oestrogen.
Adolescent↗
Failure of metoclopramide to influence LH, FSH and TSH secretion or their responses to releasing hormones.
Intravenous metoclopramide (MET) (10 mg) induced a brisk PRL response with a mean +/- SEM peak of 85.3 +/- 7.7 ng/ml maximal at 30 min. L-Dopa, but not atropine pre-treatment, attenuated the prolactin (PRL) response to MET. This indicates that the antidopaminergic properties of MET mediate PRL secretion. MET did not influence basal levels of TSH, LH or FSH. Neither did it affect their response to the respective releasing of hormones. Our results indicate that dopaminergic blockade induced by iv MET, does not influence the secretion of the pituitary glycoprotein hormones.
Adolescent↗
Metabolic clearance and plasma half disappearance time of exogenous gonadotropin releasing hormone in normal subjects and in patients with liver disease and chronic renal failure.
The metabolic clearance rate (MCR) and half disappearance time (t 1/2) of gonadotropin releasing hormone (GnRH) has been measured during and after cessation of constant infusion of exogenous GnRH. Studies were performed on normal subjects and patients with severe renal and liver disease. GnRH was quantified by a sensitive and specific radioimmunoassay which does not measure GnRH fragments. The MCR of GnRH in normal subjects was 1640+/-59.7 ml/min (23.7+/-1.8 ml/min/kg), similar to values found in 4 patients with liver disease. However in chronic renal failure an MCR of only 631+/-62 ml/min (9.1+/-0.7 ml/min/kg) was obtained. The t1/2 of GnRH after infusion was linear for 8-10 min, after which a much slower component was observed. The t1/2 of the first component ranged from 5.5 to 8 min in normal subjects, 6.5-8 min in patients with liver disease but prolonged (12-16.5 min) in patients with renal failure. It would appear that GnRH is cleared rapidly in normal subjects, that moderate liver dysfunction does not alter this, but that impaired renal function significantly prolongs the t1/2 and lowers the MCR. The kidney might be an important catabolic organ for infused GnRH; alternatively, uremia might impair catabolism non-specifically.
Adult↗
Insulin and insulin-like growth factor receptors in the nervous system.
Insulin and the insulin-like growth factors (I and II) are homologous peptides essential to normal metabolism as well as growth. These peptide hormones are present in the brain, and, based on biosynthetic labeling studies as well as evidence for local gene expression, they are synthesized by nervous tissue as well as being taken up by the brain from the peripheral circulation. Furthermore, the presence of insulin and IGF receptors in the brain, on both neuronal and glial cells, also suggests a role for these peptides in the nervous system. Thus, these ligands affect brain electrical activity, either as neurotransmitters or as neuromodulators, altering the release and re-uptake of other neurotransmitters. The insulin and IGF-I and -II receptors found in the brain exhibit a lower molecular weight than corresponding receptors on peripheral tissues, primarily caused by alterations in glycosylation. Despite these alterations, both brain insulin and IGF-I receptors exhibit tyrosine kinase activity in cell-free systems, as do their peripheral counterparts. Brain insulin and IGF-I receptors are developmentally regulated, with the highest levels appearing in fetal or perinatal life. However, the altered glycosylation of brain receptors does not appear until late in fetal development. The receptors are widely distributed in the brain, but especially enriched in the circumventricular organs, choroid plexus, hypothalamus, cerebellum, and olfactory bulb. These studies on the insulin and IGF receptor in brain, add strong support to the suggestion that insulin and IGFs are important neuroactive substances, regulating growth, development, and metabolism in the brain.
Animals↗
Insulin-like growth factors.
The insulin-like growth factors (IGF-I and IGF-II) play important roles in the regulation of growth and metabolism. While the liver is the main source of circulating IGFs, their production by numerous extrahepatic tissues suggests the existence of autocrine and paracrine modes of action in addition to typical endocrine mechanisms. The actions of the IGFs are mediated through their activation of specific cell surface receptors, primarily the IGF-I receptor, although some effects may be mediated through the IGF-II receptor and the insulin receptor. The stability of the IGFs and their interaction with their receptors are mediated by specific IGF binding proteins (IGF-BPs) which are found in the circulation and in extracellular fluids. Thus, the overall biological actions of the IGFs can be regulated by control of ligand biosynthesis, modulation of receptor levels and postreceptor signalling pathways, and changes in the levels and activity of IGF-BPs.
Animals↗
Insulin-like growth factors and their receptors in normal physiology and pathological states.
The insulin-like growth factor system, which includes the IGFs, IGF-binding proteins and IGF receptors, plays an essential role in normal growth and development, as well as the cellular differentiation of a number of other important systems, including the reproductive and immune systems. IGF action has also been implicated in several pathological conditions, including tissue repair, malnutrition, diabetes and malignancy.
Animals↗
Comparison of the counterregulatory hormone response to semisynthetic human insulin and purified porcine insulin in normal subjects and patients with type I diabetes mellitus.
The counterregulatory hormone responses to semisynthetic human insulin and purified porcine insulin were compared in 20 healthy volunteers (ten men and ten women) and 16 patients (8 men and 8 women) with type I diabetes mellitus (IDDM). In both groups blood glucose fell to similar levels following insulin administration; no difference in counterregulatory hormone response or hypoglycemic awareness was noted when comparing human to porcine insulin. However, when men were compared to women, significant differences were noted in basal glucagon, cortisol, and growth hormone levels, as well as in norepinephrine, prolactin, and cortisol responses to hypoglycemia. These differences could not be attributed to insulin species, different doses of insulin, or degree of hypoglycemia. These findings suggest that hormonal response to and awareness of hypoglycemia are similar in healthy subjects and patients with IDDM following administration of human and porcine insulin and that hormonal responses in men and women should be studied separately to avoid confusion in interpreting results arising from differences in sex.
Adult↗