Increased Plasma GH Research Articles

L-dopa stimulates release of hypothalamic growth hormone-releasing hormone in humans.

A sensitive RIA for human GH-releasing hormone-(1-44)-NH2 [hGHRH-(1-44)-NH2] was developed which allows its measurement in human plasma extracts. The assay did not detect hGHRH-(1-37)-OH or hGHRH-(1-40)-OH. A method to extract hGHRH from plasma was developed using silicic acid and acid-acetone, by which recovery of synthetic hGHRH-(1-44)-NH2 from plasma averaged 74.3%. Serial dilutions of plasma extracts gave an inhibition curve parallel with that of synthetic hGHRH-(1-44)-NH2 in the RIA system. On Sephadex G-50 columns, hGHRH-like immunoreactivity (hGHRH-LI) in plasma extracts eluted as a single peak corresponding to hGHRH-(1-44)-NH2. This hGHRH-LI peak, when subjected to reverse phase HPLC, emerged at the position where hGHRH-(1-44)-NH2 was eluted. hGHRH-LI was detectable in the peripherally circulating plasma of all subjects tested. The mean basal level of plasma hGHRH-LI in normal subjects was 9.4 +/- 0.7 (+/- SE) pg/ml (n = 22; range, 2.8-18.1 pg/ml), comparable to the basal plasma hGHRH-LI concentration in patients with hypothalamic lesions (11.3 +/- 1.1 pg/ml; n = 7). Oral administration of L-dopa (0.5 g) caused a significant increase in both plasma hGHRH-LI and GH levels in normal subjects, and the plasma hGHRH-LI peak slightly preceded or coincided with that of plasma GH in individual subjects. There was also a significant correlation between plasma hGHRH-LI and the GH rises after L-dopa administration when their net increments were compared. All of the patients with hypothalamic lesions had significant increases in plasma GH after hGHRH-(1-44)-NH2 injection (1 microgram/kg BW, iv), indicating the presence of functioning somatotrophs in their pituitaries. When L-dopa was orally administered to these patients, neither plasma hGHRH-LI nor GH concentration changed throughout a 120-min observation period. These findings suggest that 1) hGHRH, immunologically and chromatographically indistinguishable from synthetic hGHRH-(1-44)-NH2, is detectable in peripheral plasma in humans; 2) L-dopa stimulates the release of hypothalamic hGHRH, alterations of which are reflected in changes in peripheral levels; and 3) the source of circulating hGHRH is not restricted to the hypothalamus, since hGHRH-LI is present in the peripheral plasma of patients with hypothalamic lesions in amounts similar to those found in normal subjects.

Plasma growth hormone responses to microinfusion of noradrenergic agents into or electrical stimulation of the hypothalamus and amygdala in baboons.

In nine baboons (Papio papio) guide cannulae and electrodes were stereotaxically implanted into the medial basal or lateral hypothalamus, the anterior hypothalamus or the dorsal amygdala. Plasma GH responses were measured after microinfusion (1 microliter) of the alpha2 adrenergic agonist, clonidine, or the beta adrenergic antagonist, propranolol, or electrical stimulation, in each of these sites. Clonidine, 100 nmol/microliter, infused into the medial basal or lateral hypothalamus elevated plasma GH levels by 5-30 ng/ml, 30-45 min post-infusion. Plasma GH responses to clonidine infused into the anterior hypothalamus or the dorsal amygdala were all less than 10 ng/ml. The prior, intravenous, administration of piperoxane, 1.0 mg/kg prevented GH responses to clonidine. Propranolol, 50 nmol/microliter, infused into the dorsal amygdala consistently increased plasma GH levels by 5-15 ng/ml. Electrical stimulation of the medial basal or lateral hypothalamus elevated plasma GH levels by 7-35 ng/ml, 15-45 min post stimulation. Electrical stimulation of anterior hypothalamus or dorsal amygdala did not alter plasma GH levels. The stimulation of alpha 2 adrenergic receptors in the medial basal or lateral hypothalamus of the baboons appears to facilitate GH release.

Augmentation by propranolol of growth hormone-releasing hormone-(1-44)-NH2-induced growth hormone release in normal short and normal children.

The effect of a 90-min iv infusion of propranolol, a beta-adrenergic antagonist (0.2 mg/kg BW), on basal plasma GH levels and the GH responses to an iv bolus injection of GH-releasing hormone-(1-44)-NH2 (GHRH; 1 microgram/kg BW) was examined in 10 prepubertal children (6 short but otherwise normal and 4 normal). The iv injection of GHRH resulted in significant increases in plasma GH, comparable to those after either insulin-induced hypoglycemia or arginine infusion. Only a small and inconsistent increase in plasma GH levels occurred during the iv infusion of propranolol, whereas simultaneous administration of propranolol with GHRH caused marked enhancement of GHRH-induced GH release in all subjects. The difference between the plasma GH response to GHRH given with propranolol and the response to GHRH given with 0.9% saline was significantly greater than that between the plasma GH level after propranolol and that after 0.9% saline infusion without GHRH injections. There was no difference in plasma GH responses to GHRH, propranolol, or both in the normal short children or normal children. These findings indicate that beta-adrenergic blockade potentiates GHRH-induced GH secretion in prepubertal children.

Involvement of growth hormone-releasing factor in growth hormone secretion induced by gamma-aminobutyric acid in conscious rats.

Intracerebroventricular (icv) injection of gamma-aminobutyric acid (GABA) (10 mumol/rat) resulted in an increase in plasma GH in conscious freely moving rats pretreated with normal rabbit serum (0.5 ml/rat, iv). Rabbit antiserum specific for rat GH-releasing factor (GRF) (0.5 ml/rat, iv) abolished GH release induced by GABA in these animals. Rabbit anti-rat GRF serum also blunted GH release induced by a Met5-enkephalin analog, FK33-824 (10 micrograms/100 g BW, iv) in conscious rats. Considering our previous findings that rat GH release induced by FK33-824 was blunted by GABA antagonists (Endocrinology 103:1033, 1981), these results suggest that GH secretion induced by opioid peptides via GABAergic mechanisms is mediated, at least in part, by hypothalamic GRF in the rat.

Control of plasma levels of growth hormone, glucagon and insulin in ducklings: roles of free fatty acids and somatostatin.

The effects of plasma free fatty acids (FFA) and somatostatin-14 (S-14) on concentrations of plasma GH, glucagon and insulin were investigated in juvenile ducks. Oleic acid, S-14 or both were infused into 4- to 7-week-old birds and plasma GH, glucagon-like immunoreactivity (GLI), immunoreactive insulin (IRI) and FFA were measured. An increase in plasma GH and a decrease in GLI but no change in IRI was observed after infusion of 9 mg oleic acid/kg per min. A decrease in plasma GH, FFA and IRI and an increase in plasma GLI was seen after infusion of 800 ng S-14/kg per min. These effects of S-14 on IRI and GLI were abolished when S-14 was infused simultaneously with oleic acid. It is concluded that FFA have a direct stimulatory effect on GH secretion and an inhibitory effect on glucagon secretion. Somatostatin-14 directly inhibits the secretion of GH and its stimulatory effect on the secretion of glucagon is mediated by a depression in concentrations of plasma FFA. Finally, S-14 has no effect on plasma insulin when basal levels of plasma FFA are maintained.

Persistent TRH-induced growth hormone release after short-term and long-term L-thyroxine replacement therapy in primary congenital hypothyroidism.

No appreciable changes in plasma GH levels after TRH stimulation have been observed in normal subjects, whereas acute GH release has been reported in primary hypothyroidism and other pathophysiological states. To evaluate the effect of the T4 replacement therapy on TRH-induced GH release, 28 patient volunteers with primary congenital hypothyroidism (PCH), were studied before (11 subjects), after 1 month (nine subjects) and after long-term T4 replacement therapy (eight subjects). All patients underwent a TRH test with measurement of TSH, PRL and GH levels, and were compared to 28 age-matched normal subjects. An increase of plasma GH after TRH was found in 46% of patients without any therapy, in 67% of patients after one month of T4 administration and in 75% of patients after long-term therapy. No changes were observed in plasma GH levels in controls. The TSH response to TRH was inhibited and the response of PRL was reduced step by step by T4 replacement therapy in our patients with PCH. Our results suggest that: (i) Replacement T4 therapy in PCH does not abolish the paradoxical GH response to TRH, in spite of inhibiting the TSH response and reducing the exaggerated PRL response; (ii) the GH response to TRH in PCH seems to be unrelated to low thyroid hormone levels and/or to high TSH levels, but it could be due to changes in hypothalamic-pituitary regulation which are not improved by T4 replacement therapy.

Gonadotropin releasing hormone elicits abnormal hormone responses in schizophrenia

We studied the non-specific responses of GH and PRL to gonadotropin releasing hormone (GnRH) in eleven male patients aged 18–30 in whom a diagnosis of acute schizophrenia was made according to Crow's criteria. GnRH administration was followed by a significant increase in plasma GH in five patients; plasma PRL increased in two patients. The two prolactin responders were also GH responders. Non-specific GH response was confirmed on repeated testing in two patients in whom GnRH stimulation was performed twice. During saline control, non-specific hormone responses were not observed. The abnormal hormone responses observed in acute schizophrenia are probably due to the disordered monoamine regulation characteristic of this condition.

Effect of growth hormone-releasing factor on plasma growth hormone, prolactin and somatomedin C in hypopituitary and short normal children.

We studied the effect of a single intravenous bolus of 0.5 microgram/kg of growth hormone-releasing factor (GRF) on plasma GH, prolactin (PRL) and somatomedin C (SMC) in 12 short normal children and 24 patients with severe GH deficiency (GHD), i.e. GH less than 5 ng/ml after insulin and glucagon tolerance tests. GRF elicited an increase in plasma GH in both short normal and GHD children. The mean GH peak was lower in the GHD than in the short normal children (8.2 +/- 2.5 vs. 39.2 +/- 5.1 ng/ml, p less than 0.001). In the GHD patients (but not in the short normals) there was a negative correlation between bone age and peak GH after GRF (r = -0.58, p less than 0.005); GH peaks within the normal range were seen in 5 out of 8 GHD children with a bone age less than 5 years. In the short normal children, GRF had no effect on plasma PRL, which decreased continuously between 8.30 and 11 a.m. (from 206 +/- 22 to 86 +/- 10 microU/ml, p less than 0.005), a reflection of its circadian rhythm. In the majority of the GHD patients, PRL levels were higher than in the short normal children but had the same circadian rhythm, except that a slight increase in PRL was observed 15 min after GRF; this increase in PRL was seen both in children with isolated GHD and in those with multiple hormone deficiencies; it did occur in some GHD patients who had no GH response to GRF. Serum SMC did not change 24 h after GRF in the short normal children. We conclude that: (1) in short normal children: (a) the mean GH response to a single intravenous bolus of 0.5 microgram/kg of GRF is similar to that reported in young adults and (b) GRF has no effect on PRL secretion; (2) in GHD patients: (a) normal GH responses to GRF are seen in patients with a bone age less than 5 years and establish the integrity of the somatotrophs in those cases; (b) the GH responsiveness to GRF decreases with age, which probably reflects the duration of endogenous GRF deficiency, and (c) although the PRL response to GRF is heterogeneous, it does in some patients provide additional evidence of responsive pituitary tissue.

Diurnal variations of plasma growth hormone, thyrotropin, thyroxine, and triiodothyronine in streptozotocin-diabetic and food-restricted rats.

The pattern of spontaneous GH, TSH, T4, and T3 secretion has been studied in male rats in response to a 15-day period of streptozotocin diabetes or food restriction. Beginning at 0900 h, groups of control (C), food-restricted (FR), diabetic (D), and insulin-treated D rats were killed every 60-90 min for a 8-h period. Food restriction resulted in a significant depression of the GH, TSH, T4, and T3 peaks, whereas diabetes caused complete suppression of episodic secretion of each hormone. Insulin (6 U/100 g BW X day for 12 days) administration to D rats restored the normal pattern of secretion. In D and FR rats, pituitary GH concentrations were lower than in C rats, whereas pituitary TSH concentrations were similar to those in controls. Thus, as compared to C rats, FR and D rats showed an inhibition in GH, TSH, T4, and T3 secretion, most marked in D animals. Since diabetes is associated with a deficiency of circulating thyroid hormones, the potential roles of T4 and T3 on pituitary GH concentration and secretion in D rats were evaluated. Treatment of D rats with insulin (3 U/100 g BW X day), T4 (1.8 micrograms/100 g BW X day), or T3 (0.30 microgram/100 g BW X day) for 12 days resulted in a significant but limited increase in pituitary GH content. When administered together with insulin, the net effects of T4 or T3 with insulin appeared additive. T4 administration to D rats produced a significant though limited increase in plasma GH concentrations and weight gain, whereas both values were unaffected by T3. Simultaneous administration of T4 and insulin resulted in significant increased plasma GH concentration to levels greater than those in C rats. However, plasma GH levels in rats treated with T3 plus insulin were greater than those in D rats, but lower than in C animals. The results indicate that the decreased pituitary GH content of D rats can be corrected, at least in part, by T4 and T3.

Long-term follow-up of five untreated acromegalic patients

Abstract. The present study describes the clinical, biochemical and radiological follow-up of 5 patients with acromegaly, selected from a group of 53 patients, who did not receive treatment during a follow-up period of 5–16 years. The characteristics of these patients included: 1) older age (4 cases), 2) a long history of mild symptoms and signs (4 cases), 3) absence of diabetes mellitus (5 cases), 4) relatively low plasma GH levels (3 cases). The following observations were made during follow-up: clinical activity remained constant in 3 patients and lessonned in 2 patients, the lateral fossa area as calculated from a plain lateral X-ray of the skull remained constant and plasma GH levels measured during an oral glucose tolerance test remained constant in 3 cases, decreased substantially in one case and reached low levels in another case. In this last patient a reproducible increase of plasma GH was found after oral administration of a single dose of 2.5 mg bromocriptine, suggesting complete normality of GH secretion. It is concluded that acromegaly not necessarily progresses in all patients. The results re-emphasize the importance of taking the spontaneous course of pituitary adenomas into account when assessing the effect of various treatment protocols.

Pituitary growth hormone response in rats during a 24-hour infusion of growth hormone-releasing factor.

The pituitary GH response during a 24-h iv infusion of GH-releasing factor (hpGRF-44; 15 micrograms/h) and to a subsequent bolus injection of hpGRF-44 (2 micrograms) was studied in conscious, freely moving male rats pretreated with antiserum against somatostatin. Within 2 h of the initiation of the hpGRF-44 infusion, plasma GH concentrations rose from 169 +/- 16 to 2465 +/- 307 (+/- SE) ng/ml. By 6 h, plasma GH concentrations began to fall. They decreased slowly and reached a nadir of 490 +/- 107 ng/ml by 12 h. Rats infused for 24 h with hpGRF-44 failed to respond to a 2-micrograms bolus injection (iv) of hpGRF-44, whereas rats infused for 24 h with saline responded with a normal increase in plasma GH. The pituitary GH content of rats treated with saline was significantly greater than that of rats treated with hpGRF-44. These results demonstrate that the capacity of the pituitary to respond to GRF can be exhausted after the chronic administration of hpGRF-44 and that this lack of response appears to be due, in part, to a depletion of pituitary stores of GH.

Influence of gonadal steroids on age- and sex-related secretory patterns of growth hormone in the rat.

The influence of sex steroids on the pulsatile GH-secretory pattern was investigated in male and female rats of different ages. Neonatal and prepubertal gonadectomy was performed when the rats were 0-1 and 25 days old, respectively. Determinations of plasma GH levels were made in blood samples obtained from the tip of the tail or from a chronic intracardiac venous cannula. After blood sampling from the tip of the tail, maximum and minimum plasma GH levels were determined in individual rats in order to evaluate pulse height and baseline plasma GH levels. In the chronically cannulated rats the GH pulse height and plasma GH baseline levels in individual rats were determined by means of a pulse analysis computer program. Neonatal gonadectomy of male and female rats did not affect the increase in plasma GH that is observed during late prepubertal life in both sexes. However, the pulsatile, sexually differentiated, secretory pattern of GH seen in sexually mature male and female rats was modulated by gonadectomy. In adult male rats, GH was secreted in regular episodes at 3- to 4-h intervals, baseline levels being low or undetectable. After neonatal or prepubertal gonadectomy, GH baseline levels increased in comparison to the sham-operated controls. Replacement therapy with testosterone completely reversed this effect, indicating that a continuous presence of testosterone is necessary for maintaining the low baseline GH levels in adult male rats. Neonatal, but not prepubertal, gonadectomy decreased GH pulse height in male rats during adult life, suggesting that neonatal androgen secretion is a determinant for the pulse height in adult male rats. In female rats, GH pulse height was lower and baseline levels were higher than in male rats. Neonatal gonadectomy resulted in higher plasma GH pulses during puberty and decreased GH baseline levels postpubertally. There were no apparent differences in the GH-secretory patterns between male and female rats after neonatal gonadectomy. Neonatal gonadectomy of male rats decreased body weight gain as well as longitudinal bone growth, as measured in the proximal tibia by the tetracycline method. In contrast, neonatal gonadectomy of female rats resulted in a stimulation of body weight gain and longitudinal bone growth. The present results demonstrate that gonadal steroids influence GH secretion in the rat. We suggest that the sexual differentiation of the GH secretory pattern may be important for the difference in body growth between male and female rats.

A possible role of prostacyclin to stimulate prolactin and growth hormone release by hypothalamic and pituitary actions, respectively.

Prostacyclin (PGI2) (1-5 micrograms in 3 microliters 0.05 M Tris/HCl buffer, pH 7.5) and its stable metabolite, 6-oxo-PGF1 alpha, were microinjected into the third ventricle of ovariectomized rats, and plasma FSH, GH, PRL, and TSH levels were measured by RIA. Control animals received 3 microliters buffer. Injection of 5 micrograms PGI2 dramatically elevated plasma PRL values (4- to 5-fold) at 5 and 15 min, whereas the same dose of 6-oxo-PGF1 alpha produced a significant but smaller (2-fold) stimulatory effect. A delayed increase (1.5-fold) in plasma GH occurred after intraventricular PGI2 at 30 and 60 min. 6-Oxo-PGF1 alpha failed to alter GH levels. There were no alterations in plasma FSH and TSH after intraventricular injection of PGI2. Dispersed, overnight cultured cells from anterior pituitaries of ovariectomized rats were tested with 10(-4)-10(-7) M PGI2 and its metabolite. After 15 min of incubation, 3 X 10(-5) PGI2 produced a highly significant elevation in GH release (P less than 0.001), whereas there was no alteration in PRL levels. Only pharmacological doses of 6-oxo-PGF1 alpha (10(-4) M) stimulated GH release. There was no alteration in PRL release by the cultured cells even in the presence of 10(-4) PGI2. These results suggest that PGI2 stimulates PRL release by a hypothalamic action either to increase the release of PRL-releasing factor, or to decrease release of PRL-inhibiting factor, or by both mechanisms. The delayed stimulatory effect of PGI2 on the release of GH may be exerted via an effect on the anterior lobe itself, since PGI2 was effective in stimulating GH release by the incubated pituitary cells.

Stimulation of growth hormone by vasoactive intestinal polypeptide in acromegaly.

Vasoactive intestinal polypeptide (VIP) was administered as an iv bolus of 1 micrograms/kg BW to 8 acromegalic patients and in doses of 0.5 and 1 microgram/kg BW to 15 normal volunteers. Both systolic and diastolic blood pressures decreased, and pulse rate increased transiently after VIP injection. VIP stimulated PRL release from the anterior pituitary in normal subjects. Plasma PRL responses to VIP in women were dose dependent and larger than those in men. On the other hand, plasma GH levels rose markedly after VIP injection in all 6 patients with untreated acromegaly. In 2 patients studied after transsphenoidal microadenomectomy, there was no plasma GH response to VIP. In 2 other patients with inactive acromegaly as well as in normal subjects, VIP failed to affect plasma GH levels. In all 6 patients with active acromegaly, LRH (1-2 micrograms/kg BW, iv) did not increase plasma GH levels, but TRH (5-10 micrograms/kg BW, iv) caused significant increases in plasma GH, the magnitude of which was not similar to that of increases seen after VIP injection. Paradoxical GH responses to TRH were not observed in patients in the inactive phase after transsphenoidal surgery. These findings suggest that VIP stimulates GH release in vivo in acromegalic patients. A VIP test as well as a TRH test offer promise as simple and reliable techniques to evaluate the activity of acromegaly, particularly after transsphenoidal surgery.

Human pancreatic growth hormone-releasing factor stimulates release of growth hormone in conscious unrestrained male rabbits.

The effect on GH secretion of GH-releasing factor (GRF), a 44-amino acid peptide recently isolated from a human pancreatic tumor (hpGRF), was examined in conscious male rabbits. During a 6-h period (1030-1630 h) of the control study individual rabbits exhibited pulsatile GH release with a surge at 1030-1200 h, a trough at 1200-1400 h, and a second peak at 1400-1630 h. Intravenous bolus injections of 1 and 10 micrograms hpGRF caused significant and dose-related increases in plasma GH during both the period of the trough (1300 h) and the surge (1530 h), although the GH responses were obviously higher during the latter than the former period. Passive immunization with anti-somatostatin (SRIF) sheep serum resulted in a prompt increase in plasma GH immediately after an injection of the antiserum. When 0.1, 1, and 10 micrograms hpGRF were successively injected iv at 1215, 1345, and 1515 h, respectively, maximum levels of plasma GH after hpGRF in anti-SRIF sheep serum-treated rabbits were significantly higher than in animals given normal sheep serum. The plasma GH responses to 10 micrograms hpGRF, given iv only once at 1515 h in normal sheep serum-treated animals, were not different from those to 10 micrograms hpGRF injected at 1515 h after the prior administration either of the smaller hpGRF dose (0.1 micrograms, 1215 h; 1 microgram, 1345 h), nor of the large dose (10 micrograms, 1100 h). These findings suggest the following: 1) that the secretion of GH is pulsatile in conscious, unrestrained male rabbits; 2) that hpGRF is a potent secretagogue for GH release in rabbits as well as other species; 3) that the magnitude of plasma GH response to hpGRF is different according to timing of the injection during the course of pulsatile GH secretion but is not influenced by the prior administration of hpGRF (no priming effect); and 4) that the responsiveness of plasma GH to hpGRF is affected by circulating endogenous SRIF.

Synthetic hpGRF 1–40 stimulates growth hormone and inhibits prolactin secretion in normal children and children with isolated growth hormone deficiency

Intravenously administered synthetic hpGRF 1–40 at doses of 0.1, 0.33 and 1.0 μg/kg increased plasma GH in a dose-dependent fashion in 4 normal prepubertal children. hpGRF 1–40 at the dose of 1.0 μg/kg stimulated GH release, though to a lesser extent than in normals, in 7 children with isolated GH-deficiency (IGHD) but failed to do so in a patient with craniopharyngioma. In all normal children and 6 7 patients with IGHD, hpGRF 1–40 at all doses used induced a clear and sustained lowering of plasma prolactin levels; this effect was lacking in the patient with craniopharyngioma. hpGRF 1–40 had no effect on plasma FSH, LH, TSH or glucose levels nor did it influence pulse rate, blood pressure, or body temperature. These results indicate that hpGRF 1–40 is a potent stimulus to GH release in normal prepubertal children and holds promise for treatment of GH-deficient children. In addition, in both normal children and children with IGHD, hpGRF 1–40 is a potent suppressor of prolactin levels.

Ontogeny of liver somatotropic and lactogenic binding sites in male and female rats.

Developmental changes in liver somatotropic (GH) and lactogenic (PRL) binding sites were evaluated in male and female rats from birth to sexual maturity, and compared with growth velocity, plasma GH, PRL, testosterone, and estrogens. The affinity (Ka) and the concentration of these sites were determined from the analysis of equilibrium saturation curves with [125I]bovine GH and [125I]ovine PRL, incubated with liver homogenates. GH receptors rose from 6.4 fmol/mg protein at 8 days of age to 30.3 fmol/mg protein in males and 39.4 fmol/mg protein in females at 28 days. This surge occurred concomitant with the fall of plasma GH observed after birth. It preceded by about 1 week the acceleration of growth velocity and the increase of plasma GH seen at puberty. After the peak of growth velocity (42 days), GH receptors increased steadily until 120 days in females (63.8 fmol/mg protein), whereas in males they reached a concentration of 33.5 fmol/mg protein after a transient decrease to a nadir of 13.3 fmol/mg protein a day 50. From day 8 to day 35, PRL receptors in males remained at a constant level of 10.3 fmol/mg protein, whereas in females they increased progressively from 4.8 to 21.5 fmol/mg protein. Thereafter, in most pubertal males, they became undetectable, whereas plasma testosterone was rising. In contrast, PRL receptors in females increased 3-fold between day 42 (18.9 fmol/protein) and day 50 (50.2 fmol/mg protein). Between days 8 and 120, the Ka of GH and PRL receptors showed no significant changes with age and sex (GH: 0.66 X 10(9) M-1; PRL: 0.97 X 10(9) M-1). In conclusion, the rise of liver GH receptors occurring before puberty in male and female rats may be of importance for the initiation of the pubertal growth spurt. The inverse relationship between plasma testosterone and liver PRL receptors in pubertal male rats suggests that physiological concentrations of testosterone may inhibit PRL receptors. In contrast, in female rats an opposite change of PRL receptors is observed during puberty.

Effects of naloxone on the insulin and GH responses to alpha-adrenergic stimulation with clonidine.

To find if endorphins can influence hormonal responses mediated by noradrenergic pathways, we examined the effects of naloxone, an opiate receptor blocker, on the GH and insulin responses to clonidine, a drug which acts by stimulation of alpha-adrenergic receptors. Intravenous clonidine (0.15 mg in 10 min) induced a significant fall of plasma insulin and a marked increase of plasma GH. Intravenous naloxone (bolus of 1.6 mg followed by 50 micrograms/min) did not change the insulin response to clonidine, and seemed to induce only a slight delay in the GH response.

Failure of inhibition by TRH of L-Dopa stimulated GH secretion in patients with alcoholic cirrhosis of the liver.

We have investigated the effects of a single oral dose of L-Dopa (500 mg) or of an i.v. infusion of TRH (1 mg dissolved in 400 ml of saline solution) or both administered together, on GH release in men with alcoholic cirrhosis of the liver, and compared them with responses in normal subjects. The results obtained in normal subjects confirm that TRH does not modify plasma GH levels, L-Dopa elevates GH concentrations, while the administration of these two drugs together significantly inhibits GH release induced by oral L-Dopa. In contrast, in patients with alcoholic cirrhosis of the liver, the following results were obtained: 1 TRH infusion significantly increased plasma GH levels which were steadily elevated throughout the experiment; 2 oral administration of L-Dopa provoked a significant rise in blood GH over the basal values similar to that observed in normal subjects; 3 when TRH and L-Dopa are administered at the same time a GH increase like that observed after L-Dopa alone was obtained. These results clearly demonstrate that in patients with alcoholic cirrhosis of the liver the normal inhibitory effect of TRH on L-Dopa induced GH release is completely lost.

Effects of streptozotocin-diabetes and l-thyroxine treatment on TSH and GH, and circulating glucose and glycerol in thyroidectomized rats

1. 1.The response to exogenous thyroxine in thyroidectomized rats made diabetic by treatment with streptozotocin was greatly impaired, as shown by their growth retardation and the lack of increase in plasma GH and pituitary GH and TSH concentrations. 2. 2.Insulin administration partially compensated for these endocrine alterations in diabetic thyroidectomized rats. When these animals received enough exogenous thyroxine to normalize their plasma PBI and TSH levels, insulin administration did not decrease their augmented glucose and glycerol concentrations. 3. 3.These findings show the permissive action between thyroid hormones and insulin although some effects of the former counteract those of insulin.