Development of antibody to growth hormone-releasing factor.
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Antibodies↗
Biomedical subjects
M O Thorner
Publications and source records attributed to M O Thorner.
Acceleration of growth in two children treated with human growth hormone-releasing factor.
Two growth hormone-deficient children were treated with growth hormone-releasing factor for six months. The pattern of administration--1 to 3 micrograms per kilogram of body weight, given subcutaneously over one minute every three hours by infusion pump--was chosen to simulate growth hormone secretion in normal children. During the first week of therapy, both children had evidence of the metabolic effects of increased growth hormone secretion--i.e., nitrogen retention, demonstrated by decreased nitrogen excretion (P less than 0.05), and increased urinary calcium excretion (P less than 0.01). Growth hormone secretion was increased after pulses of growth hormone-releasing factor during the entire six-month period, and growth was accelerated. One child grew at a rate of 7.1 cm per year, as compared with 4.6 cm per year before therapy; the other grew at a rate of 13.7 cm per year, as compared with 2.1 cm per year before therapy, and had increased serum levels of somatomedin C. Growth hormone--releasing factor can restore growth hormone secretion and its biologic effects, including an increase in nitrogen retention, an increase in serum somatomedin C, and acceleration of linear growth in children with growth hormone deficiency. It is premature to speculate how useful this agent will prove to be in the treatment of children with growth hormone deficiency.
Calcium↗
Human pancreatic tumor GH-releasing factor.
Within the past year, three similar peptides with specific growth hormone (GH) releasing effects have been extracted from human tissue, identified, and synthesized. Human pancreatic tumor GH releasing factor (I-40)-OH (hpGRF-40) was the sole hpGRF isolated from the pancreatic tumor of a patient in Charlottesville and was the predominant peptide isolated from the pancreatic tumor of a patient in Lyon. The Lyon tumor also contained hpGRF(1-37)-OH and hpGRF(1-44)-NH2. Both immunological and biochemical data suggest that hpGRF-40 and hpGRF-44 are present in the human hypothalamus and may be the human GH releasing hormone(s) (GHRH). In cultures of rat pituitary cells, hpGRF stimulates GH but affects neither basal and dopamine-inhibited prolactin release nor basal and gonadotropin releasing hormone (GnRH)-stimulated luteinizing hormone (LH) release. hpGRF stimulates cyclic AMP production within seconds, an effect which is blocked by somatostatin. In contrast, while hpGRF stimulates phosphatidylinositol turnover in the pituitary, the effect is not inhibited by somatostatin. In the human, hpGRF-40 (1 microgram/kg) given intravenously (i.v.) stimulates GH release within 5 minutes. hpGRF-40 does not elevate serum prolactin levels, thyrotropin (TSH), LH, or corticotropin (measured indirectly through plasma cortisol), or blood glucose or plasma concentrations of insulin, glucagon, pancreatic polypeptide, cholecystokinin, gastrin, gastric inhibitory peptide, motilin, or somatostatin. When graded doses of hpGRF (0.1-10 micrograms/kg) are given i.v., no differences are noted in the maximal levels of serum GH achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenocorticotropic Hormone↗
Disorders of prolactin and growth hormone secretion.
A large range of tests is now available to help us understand, diagnose and manage GH-related growth disorders. The traditional provocative tests of GH secretion will identify short children with severe GH deficiency. However, evidence is emerging that these pharmacological tests may not be sufficiently sensitive to identify some subjects with GH deficiency arising from neurosecretory disturbance of GH release. There is a need for a simple sensitive test that will detect subtle GH secretion of this type. hGRF administration is a reliable test of GH reserve and, when used in combination with conventional tests, may help to identify GH-deficient children with hypothalamic GRF deficiency. Whether the GH responses following GRF administration reflects physiological GH secretory activity needs to be established. The diagnosis of acromegaly is made on clinical grounds. The abnormal GH responses to glucose and TRH support the diagnosis, but by themselves should not be considered to be diagnostic of acromegaly. An elevated Sm C level also helps to establish the diagnosis, although Sm C concentrations may be elevated to the same degree in pregnancy and during puberty. The use of Sm C to monitor disease activity remains to be established. Circulating GRF levels should be measured in patients with acromegaly so that ectopic production of GRF can be identified.
Acromegaly↗
Effects of in vivo gonadal hormone environment on in vitro hGRF-40-stimulated GH release.
The effects of gender and the gonadal hormone environment on basal and stimulated growth hormone (GH) release by dispersed and continuously perifused rat anterior pituitary cells were examined. Cells from intact male and diestrus day 2 female rats and from castrate male rats either untreated or treated with testosterone (T) or 17 beta-estradiol (E2) were used. Basal GH release (ng/min per 10(7) cells; mean +/- SE) by cells from diestrus day 2 female rats was less than by cells from castrate rats treated with T (4.3 +/- 0.6 vs. 11.4 +/- 2.7, respectively; P less than 0.025). No other differences in basal release were detected. Concentration-response relationships were documented between human GH-releasing factor 40 (hGRF-40; 0.03-100 nM given as 2.5-min pulses every 27.5 min) and GH release. Mean (+/- SE) overall GH release (ng/min per 10(7) cells) above base line was greater by cells from intact male rats (496 +/- 92) than by cells from castrate (203 +/- 37.3; P less than 0.0001), castrate and T-treated (348 +/- 52.8; P = 0.008), or castrate and E2-treated (58.1 +/- 6.8; P less than 0.001) male rats or by diestrus day 2 rats (68.6 +/- 9.5; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Calcium channel agonist BAY k8644 enhances anterior pituitary secretion in rat and monkey.
A calcium channel agonist BAY k8644 was applied to anterior pituitary (AP) cells in vitro. BAY k8644 (0.1-10 microM) stimulated prolactin and growth hormone (GH) release from monolayer AP cultures; the calcium channel antagonist D-600 (1-10 microM) completely blocked this effect. By utilizing a perifusion system, we observed an immediate and sustained amplification of prolactin (2.9-fold), growth hormone (2.3-fold), and luteinizing hormone (LH, 1.6-fold) release during the 1-h application of BAY k8644 (3 microM). A hypophysiotrophic peptide pulse 4 h after the BAY k8644 was removed confirmed that the cells remained responsive to their natural secretagogues. In another perifusion study 10-3,000 nM BAY k8644 produced a graded increase in prolactin release that was maintained over the 30-min exposure period. Finally, individual primate mammotrophs and somatotrophs showed a marked enlargement of hemolytic plaque area, an index of hormone release, 1 h after BAY k8644 (1 microM). We conclude that this synthetic dihydropyridine enhances the rate of prolactin, GH, and LH release from AP cells of two species. Because this is the first synthetic calcium channel agonist, structure-function studies characterizing calcium channel activation and exocytosis are now feasible.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Differential effects of forskolin on LH and GH release.
The effects of forskolin, an agent which increases intracellular levels of cAMP, on basal luteinizing hormone (LH) and growth hormone (GH) release and on gonadotropin-releasing hormone (GnRH)-stimulated LH release were documented. Continuously perifused dispersed anterior pituitary cells from female rats at random stages of the estrous cycle were used. Secretory rates of both LH and GH increased in a concentration-dependent manner in response to a 1-h challenge with 0.03, 0.1, 0.3, 1, or 3 microM forskolin. In response to 0.3 microM forskolin, maximum GH release was achieved within 15-20 min, after which secretion decreased. In contrast, LH release increased gradually, became maximal at 1.5-2 h, and remained constant until the forskolin was withdrawn. Cells exposed to 10 nM GnRH for 4 h exhibited a biphasic release of LH with the interphase nadir occurring at 30 min. The second phase of LH release was enhanced by simultaneous addition of forskolin with the GnRH. Whereas second phase release did not increase further, exposure of the cells to forskolin for 60 or 120 min before GnRH resulted in increased first-phase LH release. We suggest that, whereas our data are consistent with a role for cAMP in mediating the acute release of GH, cAMP may be involved in the process through which nonimmediately releasable LH becomes available for release.
Animals↗
Spontaneous sparsely-granulated prolactin-producing pituitary adenomas in aging rats. A prospective study of the effect of bromocriptine.
The effect of bromocriptine (BEC) treatment on spontaneous, sparsely granulated, prolactin-producing pituitary adenomas was studied in aging female Long-Evans rats of at least 23 months of age. Rats treated with BEC for 1-44 days showed a marked decrease in serum prolactin (PRL) concentrations at the end of the treatment period (9.1-34 ng/ml) when compared to the serum PRL levels of age-matched control animals (94.6-233 ng/ml). No significant differences in serum PRL levels (ng/ml; mean +/- SEM) were noted in rats withdrawn for 14 days from BEC treatment (132.9 +/- 18.8) when compared to age-matched controls (181.5 +/- 70.9). The mean pituitary weight (mg) was significantly reduced in the rats treated for 44 days with BEC (23.4 +/- 1.4) compared to untreated controls (43.4 +/- 8.3). At the time of sacrifice, PRL-producing adenomas were found in 16 of 33 control rats, 5 of 10 rats treated for 1 day with BEC, 5 of 20 rats treated with BEC for 44 days, and 12 of 28 rats in the animals withdrawn from BEC treatment for 14 days. Morphometric analysis of sparsely granulated PRL-containing adenomas revealed that, although the nuclear area was reduced after 1 day of BEC treatment, the cytoplasmic area was reduced only after 44 days. Forming granule diameters were significantly increased after 44 days of BEC treatment and markedly decreased in the withdrawal group. Storage granule diameters were increased in both the 1-day and 44-day groups and were decreased in rats withdrawn from BEC for 14 days. Rough endoplasmic reticulum, forming granule, storage granule, and lysosome volume densities were increased after 1 day of BEC treatment. The Golgi region volume density decreased only after 44 days of BEC treatment. We conclude that aging female Long-Evans rats harboring PRL-producing pituitary adenomas can respond to BEC administration with a decrease in serum PRL levels and morphologic changes in adenoma cells. However, the structural alterations in PRL cells of the rat adenomas are less conspicuous than those of human tumors. In the rat, like in human patients, a direct toxic effect of BEC on PRL-producing adenoma cells has not been demonstrated.
Adenoma↗
Pulsatile growth hormone secretion in normal man during a continuous 24-hour infusion of human growth hormone releasing factor (1-40). Evidence for intermittent somatostatin secretion.
Growth hormone (GH) secretory patterns were studied in a patient with ectopic growth hormone releasing factor (GRF) secretion and in normal men given continuous infusions of human growth hormone releasing factor (1-40)-OH (hGRF-40). In the patient with ectopic GRF secretion, GH secretion was pulsatile despite continuously elevated immunoreactive GRF levels. To determine if pulsatile GH secretion is maintained in normal subjects, we administered to six healthy young men vehicle or hGRF-40, 2 ng/kg per min, for 24 h and gave a supramaximal intravenous bolus dose of hGRF-40, 3.3 micrograms/kg, after 23.5 h of infusion. hGRF-40 infusion resulted in greater GH secretion than did vehicle infusion and pulsatile GH secretion was maintained throughout hGRF-40 infusion. During the 23.5 h of vehicle infusion, total GH secretion (microgram; mean +/- SEM) was 634 +/- 151 compared with 1,576 +/- 284 during hGRF-40 infusion (P = 0.042). The GH response to the intravenous bolus of hGRF-40 was greater after vehicle infusion than after hGRF-40 infusion; 877 +/- 170 and 386 +/- 125 micrograms of GH was secreted after the bolus on vehicle and hGRF-40 days, respectively (P = 0.015). The total amount of GH secreted during the 25.5 h of the two study days was not different; 1,504 +/- 260 and 1,952 +/- 383 micrograms were secreted during vehicle and hGRF-40 days, respectively (P = 0.36). Not only was pulsatile GH secretion maintained during hGRF-40 infusion, but there was augmentation of naturally occurring GH pulses, which is in contrast to the effect of gonadotropin-releasing hormone on gonadotropin secretion. We suggest that GH pulses are a result of GRF secretion that is associated with a diminution or withdrawal of somatostatin secretion.
Acromegaly↗
Growth hormone releasing hormone and growth hormone: genetic studies in familial growth hormone deficiency.
Four families with growth hormone (GH) deficiency, either isolated or with other pituitary hormonal deficits are described. Members of each underwent pharmacological testing for GH secretion and infusions of GH releasing hormone (GHRH) to determine the locus of the defect in GH secretion. In addition, we have extracted DNA from white blood cells to characterize the GHRH and GH genes. All members tested had the normal complement of GH and GHRH genes. Four generations of one family with isolated GH deficiency, autosomal dominant were studied. The younger members showed minimal GH responsiveness to a single infusion of GHRH. However, the older members did not respond even after 30 doses of GHRH given intravenously every 3 h. Two members of a family with the autosomal recessive type of isolated GH deficiency had large GH increases after GHRH infusion. Thus in these families the GH secretory defect lies within the hypothalamus. Members of two families with pituitary deficiency (GH and other tropic hormones) of the autosomal recessive type had variable responses to GHRH and varying amounts of pituitary tissue seen on high resolution CT scans. Although it is not possible to delineate the precise location of the secretory defects in these latter two families, a hypothalamic defect is probable based on the responses to multiple trophic stimuli. Heterogeneity of structure and function exists within and between families with isolated GH deficiency and within and among families with pituitary deficiency. It is from the study of such families in which all members presumably have the same underlying defect that one can more readily decide on a pathogenetic mechanism.
Adolescent↗
Enumeration of lactotropes and somatotropes among male and female pituitary cells in culture: evidence in favor of a mammosomatotrope subpopulation in the rat.
The hemolytic plaque assay technique can be used to detect specific hormone release from single pituitary cells. Using antisera raised against murine GH or rat PRL, we have enumerated the active lactotropes and somatotropes from male and female rat pituitary glands. These studies reveal sex-related differences in the number of cells exporting GH and PRL among anterior pituitary cells in culture. In the presence of human GH-releasing factor (hGRF), the mean percentage of GH cells was 53% in males and 30% in females (P less than 0.005). The mean percentage of PRL cells was 15% in males and 39% in females (P less than 0.008). These values were not significantly altered when hGRF was omitted. The sum of GH and PRL cells identified in separate plaque assays significantly exceeds the number obtained when GH and PRL cells were determined concurrently with a simultaneous plaque assay for both hormones. This difference is dependent on the presence of hGRF, since there was no difference when hGRF was omitted. These data identify the mammosomatotrope in numbers lower than previous reports. By this approach, the mammosomatotrope subpopulation numbers about 5% of all cells in culture. In summary, we demonstrate a sex-related difference in the number of cells exporting GH or PRL among pituitary cells in culture. This difference corresponds with and may underly sex-related differences in the responsiveness of GH and PRL secretion from the pituitary gland. Furthermore, a minor subpopulation of normal pituitary cells appears capable of simultaneous secretion of both GH and PRL.
Animals↗
Beta-adrenergic binding and secretory responses of the anterior pituitary.
Our studies demonstrated that beta-adrenergic agonists stimulate the release of GH from rat anterior pituitary (AP) cells in vitro. Concentration-response experiments with beta-adrenergic agonists demonstrated that beta 2-adrenergic receptors mediated this phasic GH release, while having no apparent effect on PRL or LH release. The ACTH response to beta-adrenergic agonists was equivocal. Half-maximal stimulation of GH release occurred at 14 +/- 2 (+/-SE) nM isoproterenol, 160 +/- 30 nM epinephrine, and over 1 microM l-norepinephrine (n = 4). Direct binding studies in membrane particulates of rat AP confirmed receptors of the beta 2-subtype. Iodocyanopindolol binding to beta-adrenergic receptors of rat AP yielded a dissociation constant of 4.6 +/- 0.1 pM and a maximal capacity of 1.9 +/- 0.4 fmol/mg protein (n = 3). In contrast, porcine AP contained beta 1-adrenergic receptors. These results support the hypothesis that the endogenous beta 2-adrenergic agonist l-epinephrine may be a GH-releasing factor of physiological significance in the rat.
Adrenocorticotropic Hormone↗
Divergent influences of the structurally dissimilar calcium entry blockers, diltiazem and verapamil, on thyrotropin- and gonadotropin-releasing hormone-stimulated anterior pituitary hormone secretion in man.
We have tested the influence of a new calcium ion channel antagonist, diltiazem, on hypothalamic releasing hormone-stimulated secretion of LH and other anterior pituitary hormones in man. To this end, six normal men received a continuous infusion of GnRH (1 microgram/min) and TRH (2 micrograms/min) for 3 h under three different experimental conditions: 1) saline (control) infusion; 2) iv diltiazem (0.3 mg/kg bolus dose, and 0.002 mg/kg . min) infusion for 4 h beginning 1 h before releasing hormone injection; and 3) oral diltiazem (60 mg, every 6 h) administration for 1 week before pituitary stimulation. Blood was sampled at 10-min intervals for the subsequent immunoassay of LH, FSH, TSH, PRL, and GH concentrations and at hourly intervals for the assay of plasma diltiazem concentrations by high performance liquid chromatography. Despite sustained plasma diltiazem concentrations of 80-120 ng/ml during either iv or oral drug administration, the GnRH/TRH-stimulated release of LH, FSH, TSH, and PRL or the basal secretion of GH did not differ significantly from that during saline infusion. In contrast, when these subjects underwent the same infusion schedule using a structurally dissimilar calcium influx blocker, verapamil (5-mg bolus dose and 15 mg/h, continuous infusion), there was significant suppression of the delayed component of GnRH/TRH-stimulated LH release, with simultaneous enhancement of PRL secretion. We conclude that exogenously stimulated anterior pituitary hormone secretion in man exhibits differential susceptibility to the structurally discrete calcium entry blockers diltiazem and verapamil. Moreover, the differential influence of these two calcium ion channel antagonists on gonadotropes is distinct from that described in cardiac and smooth muscle cells.
Administration, Oral↗
Evidence for a limited growth hormone (GH)-releasing hormone (GHRH)-releasable quantity of GH: effects of 6-hour infusions of GHRH on GH secretion in normal man.
Human GH-releasing hormone [hGHRH-40 (GHRH)] stimulates GH release in a dose-dependent fashion when administered as single iv bolus doses or as continuous 90-min infusions. However, there has been variability in the GH responses, and it appears that there are waxing and waning effects of GHRH. To address whether these are a result of the dose of GHRH, time, or intermittent changes in sensitivity of the somatotrophs, we administered 6-h infusions of vehicle and different doses of GHRH to six normal men. In addition, an iv bolus injection of GHRH was given after 5.5 h of infusion to evaluate residual GH secretory capacity. The subjects were given infusions of either vehicle or GHRH (1, 3.3, and 10 ng/kg X min), followed by an iv bolus injection of 3.3 micrograms/kg on four separate occasions. GHRH infusions stimulated GH secretion compared to basal secretion. The changes from basal GH secretion (mean +/- SEM) were 2.0 +/- 1.6, 4.6 +/- 1.5, 12.7 +/- 5.1, and 8.2 +/- 1.8 ng/ml X h during the vehicle and GHRH (1, 3.3, and 10 ng/kg X min) infusions, respectively. The changes from basal GH secretion for 2 h after the iv bolus dose (after 5.5 h of infusion) were 33.3 +/- 8.7, 22.4 +/- 3.8, 14.0 +/- 3.6, and 10.5 +/- 2.0 ng/ml X h on the vehicle and GHRH (1, 3.3, and 10 ng/kg X min) infusion days, respectively. The magnitude of the GH response was inversely related to the GHRH infusion dose. The total amount of GH released during the 7.5-h study periods was not different among the vehicle and 3 GHRH infusion days. Thus, it appears that a finite amount of GH is released by GHRH. There was variability in the degree of responsiveness to the continuous infusions of GHRH. Surges of GH release occurred during the GHRH infusions, which may be attributed to intermittent secretion of a GH inhibitor, such a somatostatin.
Adult↗
Immunohistological localization of growth hormone-releasing hormone in human tumors.
Two forms of GH-releasing factor (GHRH), which play a role in the regulation of GH secretion, have been isolated from pancreatic endocrine tumors in two patients with acromegaly. We examined formalin-fixed, paraffin-embedded human tissues from autopsies and surgical specimens for the presence of human pancreatic GHRH-40 using the avidin-biotin-peroxidase complex technique to assess the prevalence of tumors containing GHRH, to define their primary sites and cellular derivations, and to correlate clinical and pathological features. Immunopositivity was demonstrated in 4 of 24 pancreatic endocrine tumors, 1 of 5 bronchial and 2 of 15 gut carcinoids, 1 of 2 thymic carcinoids, 2 of 20 medullary carcinomas of the thyroid, 1 of 12 pheochromocytomas, and 5 of 20 small cell carcinomas of the lung. Of the GHRH-containing tumors, only 2 of the pancreatic endocrine tumors and the bronchial carcinoid were associated with acromegaly. No GHRH was found in 35 tumors derived from cells that are not known to produce peptide hormones. Immunoreactivity was not detected in the nontumorous tissues from which GHRH-containing tumors were derived. It can be concluded that GHRH may be found in a variety of tumors arising from and composed of peptide hormone-producing endocrine cells. The significance of immunoreactive GHRH detected in tumors unassociated with clinical evidence of acromegaly remains to be established.
Acromegaly↗
Rapid sequential intravenous administration of four hypothalamic releasing hormones as a combined anterior pituitary function test in normal subjects.
Normal subjects were studied to test the feasibility of a combined anterior pituitary function test using iv administration of four hypothalamic releasing hormones: ovine corticotropin-releasing hormone, human GH-releasing hormone, GnRH, and TRH. Initially, nine normal men were studied with various combinations of these four hormones to exclude the possibility that they might inhibit or synergize with each other in releasing the individual anterior pituitary hormones. When given in combination, the releasing hormones were administered as sequential 20-sec iv infusions in the following order and doses: ovine corticotropin-releasing hormone, 1 microgram/kg; GnRH, 100 micrograms; human GH-releasing hormone, 1 microgram/kg; and TRH, 200 micrograms. Plasma or serum samples were assayed for ACTH, cortisol, GH, PRL, FSH, LH, and TSH at multiple times for 120 min after injection. Compared to individual administration, combined administration of these four hypothalamic releasing hormones caused no apparent inhibition or synergism with respect to the individual hormone responses of these normal subjects. Side-effects of the combined test were the same as those observed with individual hormone administration. No unusual or dangerous side-effects were observed. Having confirmed the efficacy of combined administration of the four releasing hormones, we administered the combination to five additional normal men and 12 normal women. Anterior pituitary hormone and cortisol responses were the same in men and women, except for a lower LH and a greater PRL response in women. There was a rapid increase in all hormones, with peak levels usually reached by 60 min. Adequate assessment of individual hormone responses can be achieved by assaying a basal and only 2 (or 3 in the case of ACTH and GH) postinfusion samples. A rapid, safe, and useful test of combined anterior pituitary function appears to be feasible using these four hypothalamic releasing hormones.
Adrenocorticotropic Hormone↗
Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study.
To assess the effectiveness of bromocriptine in reducing the size of PRL-secreting macroadenomas with extrasellar extension, we conducted a prospective multicenter trial in patients without prior radiotherapy, applying a standard protocol of treatment and tumor size evaluation. Basal serum PRL levels [1441 +/- 417 (+/- SEM) ng/ml for women; 3451 +/- 1111 ng/ml for men] fell in all patients and to 11% or less of basal values in all patients but 1. Normal PRL levels were reached in 18 of the 27 patients. In 13 patients (46%), tumor size was reduced by greater than 50%, in 5 patients (18%) by about 50%, and in 9 patients (36%) by approximately 10-25%. The extent of tumor size reduction did not correlate with basal PRL, nadir PRL, percent fall in PRL, or whether PRL levels reached normal. However, a reduction in PRL levels always preceded any detectable change in tumor size. In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, such reduction was not noted until the 6 month evaluation. In the 4 patients in whom bromocriptine was discontinued at the end of 1 yr, tumor reexpansion occurred in 3. Visual fields improved in 9 of the 10 patients in whom they were abnormal. Because of the excellent results found in most of the patients in this series, we suggest that therapy with bromocriptine should be considered as initial management for patients with PRL-secreting macroadenomas.
Adenoma↗
Blunted growth hormone (GH) response to GH-releasing hormone in hypothyroidism resolves in the euthyroid state.
GH secretion is dependent upon thyroid hormone availability. In this study, the GH response to GH-releasing hormone (GHRH) was studied in a group of patients when they were hypothyroid and also when they were euthyroid. Hypothyroidism was associated with a significant reduction in both the peak GH response and the integrated GH secretory response to GHRH compared to those in the euthyroid state [4.7 +/- 1.6 (+/- SEM) vs. 12.2 +/- 3.9 ng/ml (P less than 0.025), and 349 +/- 116 ng vs. 986 +/- 304 ng ml-1 min-1 (P less than 0.025), respectively]. GH responsiveness was impaired within 2 weeks of discontinuation of T3 treatment in athyreotic subjects and was restored within 4 weeks of T4 treatment in one chronically hypothyroid subject. The results imply that a blunted GH response to GHRH in hypothyroidism is attributable to a primary pituitary defect that occurs rapidly and is reversible with attainment of the euthyroid state.
Adult↗