Growth hormone (GH) response to GH-releasing hormone in children with subnormal integrated concentrations of GH.

We determined the GH responses to human GH-releasing hormone-40 (GHRH) in poorly growing children who had either normal or deficient GH secretion, as measured by pharmacological stimulation and integrated concentration of GH (IC-GH). Ten patients had both normal pharmacologically stimulated GH and IC-GH (GH-normal), 15 patients had normal pharmacologically stimulated GH but deficient IC-GH [GH neurosecretory dysfunction (GHND)], and the remaining 7 patients had both subnormal stimulated GH and IC-GH [GH deficiency (GHD)]. The mean peak plasma GH response to GHRH was 11.

Dual effects of growth hormone (GH)-releasing hormone infusion in normal men: somatotroph desensitization and increase in releasable GH.

Continuous infusion of human GH-releasing hormone (GHRH) stimulates GH secretion in normal subjects, but a single supramaximal iv dose of GHRH thereafter elicits a diminished serum GH response compared to that after a saline infusion; the response to the single dose challenge is inversely related to the dose of GHRH previously infused. To determine if this attenuated GH response is a result of depletion of available GH or desensitization of the somatotroph, a 6-h infusion of saline or GHRH (10 ng/kg . min) was administered to 10 normal men, and an iv bolus dose of either GHRH (3.

Medianosomes as integrative units in the external layer of the median eminence. Studies on grf/catecholamine and somatostatin/catecholamine interactions in the hypothalamus of the male rat.

Somatostatin/catecholamine as well as growth hormone releasing factor/catecholamine interactions have been characterized in the hypothalamus and the preoptic area using morphometrical and quantitative histofluorimetrical analyses. The combined results of the present and previous studies have led us to put forward the medianosome concept. The medianosome is defined as an integrative unit, which consists of well defined aggregates of transmitter identified nerve terminals interacting with one another in the external layer of the median eminence.

Morphologic effects of bromocriptine on spontaneously occurring pituitary prolactin-cell hyperplasia in old Long-Evans rats.

The effect of bromocriptine (BEC), a dopaminergic agonist, on nontumorous pituitary prolactin (PRL) cells of aging female Long-Evans rats, was studied histologically, immunocytologically, electron-microscopically, and morphometrically. Rats were arbitrarily divided into two control groups, one with normal (less than 20 ng/ml) and one with elevated serum PRL concentrations, and into four BEC-treated groups, all of which had increased serum PRL levels prior to commencement of BEC administration. In hyperprolactinemic control rats, compared with normoprolactinemic control rats, pituitary weight and percentage of pituitary PRL cells were increased.

Clinical studies with GHRH in man.

GHRH was isolated from two GHRH-secreting pancreatic tumors which resulted in clinical acromegaly. Over 98% of acromegalic patients have a pituitary adenoma; however, acromegaly may occasionally result from ectopic or eutopic GHRH secretion. Administration of GHRH to normal adults stimulates growth hormone (GH) secretion; it may also stimulate GH release in some adults with GH deficiency in childhood and in a majority of GH-deficient children.

Growth hormone releasing factor and somatomedin C production: extrahypothalamic localization and possible functional significance.

Growth hormone-releasing factor (GRF) is found in the highest concentration (albeit lower compared to other hypothalamic regulatory hormones) in the hypothalamus. There is mounting evidence that GRF-like immunoreactivity is found in other sites in the CNS and in the periphery. The role of GRF, other than to stimulate growth hormone secretion by the somatotroph, is unknown.

Effects of intravenous, subcutaneous, and intranasal administration of growth hormone (GH)-releasing hormone-40 on serum GH concentrations in normal men.

In addition to stimulating GH release in normal subjects, GH-releasing hormone-40 (GHRH-40) stimulates GH secretion in some adults and children with GH deficiency. Recognizing that GHRH-40 may have potential as a therapeutic agent for the treatment of GH deficiency, we examined the effects of iv, sc, and intranasal (in) GHRH-40 administration on GH secretion and measured the plasma levels of immunoreactive GHRH achieved after the administration of the peptide via these different routes. Normal men were given vehicle or GHRH-40 iv (0.

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.

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.

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.

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.

Altered neuroendocrine regulation of gonadotropin secretion in women distance runners.

We tested the hypothesis that the neuroendocrine control of gonadotropin secretion is altered in certain women distance runners with secondary amenorrhea. To this end, we quantitated the frequency and amplitude of spontaneous pulsatile LH secretion during a 24-h interval in nine such women. The ability of the pituitary gland to release LH normally was assessed by administration of graded bolus doses of GnRH during the subsequent 8 h.

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.

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.

Follicle-stimulating hormone- and alpha-subunit-secreting pituitary tumor treated with bromocriptine.

Glycoprotein-secreting pituitary tumors are uncommon. With increased awareness that pituitary tumors may secrete FSH, LH, TSH, and the alpha-subunit, either as a sole product or in any combination, these tumors are more likely to be recognized. The standard therapy is surgical resection and, possibly, postoperative radiotherapy for residual tumor mass or persistent hormonal secretion.

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.

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.

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.

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.

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.

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.

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.