Plasma GH Levels Research Articles

Clonidine monotherapy of a patient with mixed bipolar disorder and mania: Changes in symptomatology and neurochemical variables

1. 1. The authors report the effect of clonidine on one patient with mixed bipolar disorder resistant to treatment with neuroleptics and antidepressants. The patient improved with a daily dose of 0.45 mg. 2. 2. A manic relapse of the patient, still on clonidine, was successfully treated by increasing the clonidine dose to 0.6 mg per day. 3. 3. During the treatment the main metabolites of norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG), of dopamine homovanillic acid (HVA) and of serotonin 5-hydroxy-indoleacetic acid (5-HIAA) were assessed in urine samples. Plasma GH and PRL levels were aslo estimated. 4. 4. After initiation of clonidine regimen MHPG and HVA excretion declined whereas 5-HIAA remained unaltered. The levels of all three metabolites showed a marked increase at the onset of a manic relapse and were reduced after the increase of clonidine dose and the amelioration of manic symptoms. 5. 5. Plasma GH and PRL levels did not exhibit any considerable changes.

Acute, oral ethanol administration suppresses episodic growth hormone secretion in the male rat.

The effect of single dose ethanol administration on GH secretion was studied in young adult male rats bearing indwelling gastric and right-atrial cannulas. Rats (nonfasted) received saline or ethanol (1, 2, 3, or 4 g/kg) via gastric cannula 2h before the onset of the daily dark period; blood was sampled every 15 min for 5 h. Each rat served as its own control, receiving saline and one ethanol dose separated by 2-3 days. Plasma samples were assayed for ethanol, GH, and testosterone. On saline days, all rats showed typical, episodic peaks of GH in plasma. This pattern was unaffected by ethanol at 1 g/kg (peak plasma ethanol approximately 65 mg/100 ml). Ethanol at 2 g/kg caused a rapid, marked, but not total suppression of plasma GH levels (peak plasma ethanol approximately 140 mg/100 ml), whereas at doses of 3 or 4 g/kg ethanol, a total suppression of GH secretion occurred (peak plasma ethanol approximately 190 and 240 mg/100 ml, respectively). Plasma testosterone levels showed a similar dose-sensitivity to ethanol. The threshold for GH suppression appears to be around 100 mg/100 ml plasma ethanol and is sustained throughout the time period examined, despite falling ethanol levels.

Acute, oral ethanol administration suppresses episodic growth hormone secretion in the male rat

The effect of single dose ethanol administration on GH secretion was studied in young adult male rats bearing indwelling gastric and right-atrial cannulas. Rats (nonfasted) received saline or ethanol (1, 2, 3, or 4 g/kg) via gastric cannula 2h before the onset of the daily dark period; blood was sampled every 15 min for 5 h. Each rat served as its own control, receiving saline and one ethanol dose separated by 2-3 days. Plasma samples were assayed for ethanol, GH, and testosterone. On saline days, all rats showed typical, episodic peaks of GH in plasma. This pattern was unaffected by ethanol at 1 g/kg (peak plasma ethanol approximately 65 mg/100 ml). Ethanol at 2 g/kg caused a rapid, marked, but not total suppression of plasma GH levels (peak plasma ethanol approximately 140 mg/100 ml), whereas at doses of 3 or 4 g/kg ethanol, a total suppression of GH secretion occurred (peak plasma ethanol approximately 190 and 240 mg/100 ml, respectively). Plasma testosterone levels showed a similar dose-sensitivity to ethanol. The threshold for GH suppression appears to be around 100 mg/100 ml plasma ethanol and is sustained throughout the time period examined, despite falling ethanol levels.

A re-evaluation of the prolactin-releasing activity of growth hormone-releasing hormone in acromegaly in vivo

In 1985, Losa et al reported that an i.v. bolus injection of GH-releasing hormone (GHRH) was able to paradoxically stimulate PRL secretion in more than half of their acromegalic patients. However, this observation was not generally accepted since several other investigators have concluded that such an anomalous PRL response to GHRH was an extremely rare phenomenon in acromegaly. Therefore, in this study we examined a large number (51 patients) of active acromegalics in order to obtain more reliable data on the incidence of the paradoxical PRL response to GHRH in this disorder. Each patient underwent i.v. bolus injections of GHRH (100 μg) and thyrotropin-releasing hormone (TRH, 500 μg) on separate days, and plasma levels of GH and PRL were measured. The plasma PRL response to GHRH was considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. We found that only 6 patients (12%) showed a positive PRL response to GHRH. These PRL-responders to GHRH had higher GH responses to this peptide than PRL-non-responders to GHRH. Although PRL-responders and non-responders to GHRH had a similar PRL responsiveness to TRH, the GH response to TRH was lower in PRL-responders to GHRH than PRL-non-responders to this peptide. In addition, PRL-non-responders to GHRH had lower basal GH and higher basal PRL levels than PRL-responders to GHRH. These results suggest that the alleged PRL-releasing activity of GHRH in acromegaly may be much weaker than was originally reported by Losa et al, and the positive PRL response to GHRH may be associated with a relatively high GH response to this peptide, and also with a relatively low GH response to TRH. However, the functional significance and underlying mechanism of the positive PRL response to GHRH in acromegaly remain to be determined.

Expression of insulin-like growth factor I in normally and abnormally developing coho salmon (Oncorhynchus kisutch).

Changes in levels of insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) in tissues of normally and abnormally growing (stunted) juvenile coho salmon in seawater were studied. Profiles of hepatic IGF-I mRNA levels were compared with changes in growth and plasma concentrations of GH and insulin. In normally growing fish, IGF-I mRNA levels, as measured by solution hybridization-RNase protection assay, showed that hepatic IGF-I mRNA levels of yearling salmon were highest in May and June. Increased hepatic IGF-I mRNA levels followed increases in both plasma GH and insulin. Levels of hepatic IGF-I mRNA decreased in July, after a sharp decline in plasma GH in June, and remained low until the following spring. The growth rate for normal fish also decreased during fall and winter. After increases in plasma GH and insulin, which peaked in late February, hepatic IGF-I mRNA levels increased rapidly and reached a second peak in April. Increases in plasma GH and hepatic IGF-I mRNA observed in the second year were smaller and occurred earlier than in the first spring in seawater. Growth retardation (stunting) resulted from the premature transfer of cultured fish to seawater. Compared with normally growing fish, these stunted salmon had significantly higher levels of plasma GH but lower levels of plasma insulin. Hepatic IGF-I mRNA levels in stunted salmon were significantly lower, despite elevated plasma GH levels. These results indicate that hepatic levels of IGF-I mRNA in juvenile coho salmon increase in springtime, after an increase in plasma GH and insulin. These seasonal increases in GH and IGF-I precede the rapid growth period coinciding with the springtime increases in temperature and photoperiod and may therefore be associated with these environmental cues. The elevated plasma GH and reduced hepatic IGF-I mRNA levels observed in growth-retarded salmon suggested that stunted salmon may be GH resistant. Hepatic GH resistance and diminished IGF-I production may be the central endocrine defects leading to growth retardation in stunted salmon.

Decreased binding of growth hormone in the rat hypothalamus and choroid plexus following morphine treatment

Male Sprague-Dawley rats were continuously infused with morphine through subcutaneously implanted mini-osmotic pumps over a period of 5 days. The binding of rat growth hormone (rGH) to specific sites in choroid plexus, cortex, hypothalamus, hippocampus and striatum was determined. It was found that in the acute phase of morphine administration the density of growth hormone-binding sites was significantly decreased in choroid plexus and in hypothalamus, but not in any other of the tissues studied. When tolerance to morphine was developed, the level of growth hormone-binding was restored to control level. In the acute phase, the plasma levels of GH, as measured by radioimmunoassay, correlated negatively with the density of the binding sites in choroid plexus and hypothalamus. The decrease in growth hormone-binding in these regions of the rat brain was also confirmed by SDS-polyacrylamide gel electrophoresis of cross-linked complexes of the binding entities to 125I-labelled rGH as visualized by autoradiography. In experiments, where morphine was administrated by intermittent injections, a similar decrease in rGH-binding was observed. However, the time-course of this decrease seemed to be dependent upon the route of administration. Following intracerebroventricular (i.c.v.) injections, the binding of the hormone was already affected after 30 min, whereas the binding of rGH in brain areas after subcutaneous (s.c.) injections was affected at a later stage.

Effect of actively immunizing sheep against growth hormone-releasing hormone or somatostatin on spontaneous pulsatile and neostigmine-induced growth hormone secretion.

The physiological role of endogenous circulating GH-releasing hormone (GHRH) and somatostatin (SRIH) on spontaneous pulsatile and neostigmine-induced secretion of GH was investigated in adult rams actively immunized against each neuropeptide. All animals developed antibodies at concentrations sufficient for immunoneutralization of GHRH and SRIH levels in hypophysial portal blood. In the anti GHRH group, plasma GH levels were very low; the amplitude of GH pulses was strikingly reduced, although their number was unchanged. No stimulation of GH release was observed after neostigmine administration. The reduction of GH secretion was associated with a decreased body weight and a significant reduction in plasma IGF-I concentration. In the anti-SRIH group, no changes in basal and pulsatile GH secretion or the GH response to neostigmine were observed as compared to controls. Body weight was not significantly altered and plasma IGF-I levels were reduced in these animals. These results suggest that in sheep, circulating SRIH (in the systemic and hypophysial portal vasculature) does not play a significant role in pulsatile and neostigmine-induced secretion of GH. The mechanisms of its influence on body weight and production of IGF-I remain to be determined.

Chronic intravenous infusion of chicken growth hormone increases body fat content of young broiler chickens

The purpose of this study was to determine the effects of programmed intravenous infusion of chicken growth hormone (cGH) on growth and metabolism of young broiler chickens (4-7 weeks of age). Four-week-old broiler cockerels, fitted with indwelling jugular catheters, were randomly assigned to three treatment groups (6 birds/group): pulsatile infusion of buffer (phosphate buffer, pH 7.4)[PB-P] at 3 hr intervals, pulsatile infusion of cGH (15 micrograms/kg at 3 hr intervals)[GH-P], or continuous infusion of cGH (120 micrograms/kg-day)[GH-C]. Birds were bled 5 min before (0-min) and 5 min post-infusion (relative to the pulses of PB and cGH) at 5, 6, and 7 weeks of age. Pulsatile infusion of cGH increased (P < 0.05) feed consumption by 24% and reduced (P < 0.05) feed efficiency by 14% without affecting body weight (BW) gain. The relative weights (%BW) of liver, abdominal fat, and bursa of Fabricius were not affected by the pattern of cGH infusion. However, the body fat content of cGH-infused chickens was increased (P < 0.05) by 13% (GH-C) and 17% (GH-P), while body protein and water contents were slightly reduced. Body ash content was not affected by pattern of cGH infusion. When compared with the PB-P controls, the GH-P treatment depressed (P < 0.05) hepatic GH-binding activity by 52% without affecting plasma insulin-like growth factor-I (IGF-I) levels. Continuous infusion of cGH increased (P < 0.05) plasma IGF-I by 16%, thyroxine (T4) by 31%, and glucagon levels by 55%, although plasma GH levels were only 47% higher than those of the PB-P group. However, the GH-P treatment was only half as effective as the GH-C pattern in elevating plasma levels of T4 and glucagon. This study shows that programmed intravenous infusion of cGH increases deposition of body fat in young rapidly-growing broiler chickens.

Serum lipoproteins in acromegaly before and 6-15 months after transsphenoidal adenomectomy.

Acromegaly is a rare disorder characterized by over-secretion of GH, most often because of a pituitary adenoma. The disease is associated with disturbances in lipoprotein metabolism and an increased cardiovascular mortality. The aim of the present study was to investigate whether treatment of acromegaly results in changes in serum concentrations of lipids and apolipoproteins, including lipoprotein(a) (Lp(a)). Fourteen patients with clinical features of acromegaly and increased GH secretion were studied 1-10 months before and 6-15 months after transsphenoidal adenomectomy in an open study. Three patients had diabetes mellitus before surgery and two of these patients had normalized serum glucose levels post-operatively. Mean and baseline plasma GH levels were determined from 24-hour GH profiles. Serum samples were taken in the morning after an overnight fast. All patients were normocholesterolaemic, and four patients were hypertriglyceridaemic before treatment. Mean plasma GH levels decreased from 34.5 +/- 7.4 to 2.1 +/- 0.4 mU/l (mean +/- SEM). Serum IGF-I, insulin and free T3 levels decreased and serum SHBG concentrations increased post-operatively. There was no effect of treatment on serum cholesterol concentrations, but serum triglyceride concentrations decreased. Serum apolipoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA-I levels increased and Lp(a) levels decreased post-operatively. Successful treatment of acromegaly, resulting in normal mean GH values (< 5 mU/l) and/or normal responsiveness to TRH, have beneficial effects on serum lipoproteins with increased serum apoA-I levels and decreased serum levels of triglycerides and Lp(a). These effects seem to be independent of improvement in glucose tolerance, since patients with diabetes mellitus before surgery and normal fasting blood glucose levels post-operatively had similar lipoprotein responses to treatment as those with normal fasting blood glucose levels before surgery.

Inhibition of growth hormone release after the combined administration of GHRH and GHRP-6 in patients with Cushing's syndrome.

In patients with Cushing's syndrome there is a blunted GH response to all types of stimuli. Although inferential data point towards a direct perturbation in the pituitary exerted by glucocorticoids, the basic mechanism is unknown. His-D-TRP-ALA-TRP-D-Phe-Lys-NH2 (GHRP-6) is a synthetic hexapeptide which releases GH by a direct pituitary effect through receptors other than GHRH receptors. Furthermore, the combined administration of GHRH and GHRP-6 is able to induce a large GH discharge even in some pathological states such as obesity, associated with GH blockade. To gain further insight into the disrupted mechanisms of GH secretion, Cushing's syndrome patients were challenged with either GHRH, GHRP-6 or GHRH together with GHRP-6. A group of normal subjects was included for control purposes. Three different tests were undertaken: (a) GHRH 100 micrograms i.v.; (b) GHRP-6 100 micrograms i.v. and (c) GHRH plus GHRP-6 100 micrograms i.v. of each; administered to each subject on different days, at least 4 days apart. Ten patients (8 women, 2 men) with untreated Cushing's syndrome, 9 Cushing's disease and 1 adrenal adenoma. Five healthy volunteers (3 women, 2 men) of similar ages served as a control group. Plasma GH levels were measured by immunoradiometric assay. The areas under the curve (AUC) of GH secretion (mean +/- SEM in mU/I/120 min) in the control subjects after each test were: GHRH, 1420 +/- 330; GHRP-6, 2278 +/- 290 and GHRH plus GHRP-6, 7332 +/- 592 (P < 0.05 vs each compound alone). The AUCs for Cushing's syndrome patients were: GHRH, 248 +/- 165; GHRP-6 530 +/- 170 and for GHRH plus GHRP-6, 870 +/- 258 (P < 0.05 vs GHRH alone). After the combined stimulus only one out of the ten patients with hypercortisolism showed a GH peak over 20 mU/I, while all the controls had a peak over 84 mU/I. GHRP-6 induced GH secretion as well as the GH discharge elicited by GHRH and GHRP-6 are considerably reduced in Cushing's syndrome patients. This suggests that the main impairment of GH secretion in that pathological state resides at pituitary level.

Pharmacokinetic and pharmacodynamic properties of a long‐acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.

1. The aims of the study were to assess the pharmacokinetic parameters and the hormonal effects of the slow-release formulation of the somatostatin analogue (SR-L) in normal male volunteers. 2. Eight healthy males were studied. For the determination of basal values blood was sampled before the injection of vehicle and then every other hour for 8 h in order to measure plasma GH, prolactin (PRL), TSH, free thyroxin (fT4), insulin and glucagon levels. Plasma insulin-like growth factor 1 (IGF-1) levels were measured on a single sample. On day 1 of the study, 30 mg SR-L was administered intramuscularly. Blood was drawn just before injection and then every other hour for a period of 8 h. Thereafter, blood was sampled three times a week for 3 weeks in order to measure lanreotide, IGF-1, TSH, fT4 and PRL concentrations. Plasma GH was determined on days 6 and 11 of the study. 3. Plasma lanreotide concentrations rose to 38.3 +/- 4.1 ng ml-1 2 h following injection. The levels then progressively decreased, remaining above 1.5 ng ml-1 until day 11 and reaching 0.92 +/- 0.28 ng ml-1 2 weeks after injection. The apparent plasma half-life and mean residence time were 4.52 +/- 0.50 and 5.48 +/- 0.51 days respectively. 4. By comparison with the control day, plasma insulin concentrations only decreased 2 h following injection, whereas plasma glucagon did not change at any time. 5. Plasma TSH concentrations were significantly (P < 0.01) reduced from 2 h to day 4 following SR-L injection.2+ '

Anomalous growth hormone response to vasoactive intestinal peptide and peptide histidine methionine in patients with prolactinoma or hypothalamic hyperprolactinemia

We examined a possible GH-releasing activity of vasoactive intestinal peptide (VIP) and its homologous peptide, peptide histidine methionine (PHM), in 22 patients with hyperprolactinemia (HPRL) who comprised 19 cases of prolactinoma (PRLoma) and 3 cases of hypothalamic HPRL. Each patient underwent iv bolus injections of VIP (100 μg) and PHM (100 μg) on separate days, and plasma levels of GH and PRL were measured. The plasma GH response to VIP and PHM were considered positive (a paradoxical increase) when an increase over baseline of at least 50% occurred. In agreement with previous reports, the PRL-releasing activity of VIP and PHM in our patients with HPRL were subnormal. Thirteen (59%) patients showed a paradoxical rise in GH after VIP, and 4 (18%) patients did so after PHM. It is to be noted that all the 3 patients with hypothalamic HPRL responded to VIP with a significant rise in GH. 3 of the 4 PHM-responders were also responsive to VIP, which suggests that PHM may have activated VIP receptors in the pituitary of the PHM-responders as a partial agonist of the VIP receptor. The responders and nonresponders to VIP or PHM, respectively, had similar results with respect to the mean age, and the mean basal PRL and GH levels in the plasma. Since these paradoxical GH responses were observed in not only the patients with PRLoma but also those with hypothalamic HPRL, it may be that these anomalous GH responses in HPRL were due to the HPRL itself rather than due to the neoplastic lactotrophs. Although the pathophysiological significance of this phenomenon is open to question, it is suggested at least that VIP and/or PHM receptors may anomalously appear on somatotrophs in the pituitary of at least some patients with HPRL.

Slow release lanreotide treatment in acromegalic patients previously normalized by octreotide.

Several clinical studies reported the efficacy of the long-acting SRIH analog, octreotide (Octreotide, Sandoz) in the treatment of acromegaly. Recently, another SRIH analog (BIM 23014, Ipsen Biotech) was shown to decrease plasma GH levels in acromegalic patients. The recent availability of a long-acting formulation of BIM 23014 [slow release (SR) lanreotide] could avoid the inconveniences associated with either repeated sc injections or continuous sc infusions. In this study, we compared the clinical and biochemical efficacies of both drugs in a cohort of 19 acromegalic patients, considered initially as responsive to octreotide and sequentially treated with octreotide (3 sc injections of 100-200 micrograms/day) for 12 months and with SR lanreotide (30 mg, im, every 10 or 14 days) for 6 months. Before octreotide treatment, baseline plasma GH (mean +/- SE of 8 hourly samplings) was 29.0 +/- 10.0 micrograms/L and was lowered to 3.2 +/- .2 micrograms/L during the first 7 h after the first 100-micrograms sc octreotide administration. After 12 months of treatment with octreotide, 14 of 19 patients (74%) were considered normalized, as their mean individual GH profiles and insulin-like growth factor-I (IGF-I) values were within the normal range. After octreotide withdrawal for 1 week, plasma GH and IGF-I levels rose to 18.3 +/- 4.8 and 4.1 +/- 0.4 U/mL, respectively. The first 30-mg SR lanreotide im injection produced an acute suppression of plasma GH levels (mean GH value during the 7 h after the injection, 3.0 +/- 0.4 micrograms/L), not different from results previously observed after the first octreotide injection. After 3 months of treatment with 30 mg SR lanreotide every 14 days, normalization of baseline GH and IGF1 levels was achieved in 6 of 19 patients. Ten patients, who did not achieve normal GH levels, subsequently received a 30-mg SR lanreotide injection every 10 days. Among them, normalization of GH and IGF-I levels occurred in 7 of 10 patients after 3 months of such a regimen. After 6 months of SR lanreotide treatment, 13 of 19 patients (68%) were considered normalized, with mean GH and IGF-I values, respectively, of 3.1 +/- 0.4 micrograms/L and 1.5 +/- 0.1 U/mL. The overall tolerance of both drugs (glucose homeostasis and gallstone formation) was similar.(ABSTRACT TRUNCATED AT 400 WORDS)

Pulsatile infusion of growth hormone-releasing factor depresses growth of young broiler chickens

This study was conducted to determine the effects of programmed intravenous infusion of growth hormone-releasing factor (GRF) on the growth and metabolism of young broiler chickens (4–7 weeks of age). Twelve 4-week-old chickens, fitted with jugular catheters, were randomly assigned to three treatment groups (four birds/group): pulsed infusion of saline [SAL-P] at 3 hr intervals, pulsed infusion of GRF 1–44 (5μg/kg at 3 hr intervals)(GRF-P], or continuous infusion of GRF (40 μg/kg-day)(GRF-C]. The GRF-P treatment depressed ( P < 0.05) average daily gain by 32%, average daily feed consumption by 24%, and final body weight by 17% when compared with the SAL-P group. Pulsatile infusion of GRF (GRF-P) reduced ( P < 0.05) abdominal fat weight by 39% and body fat content by 28% when compared to the SAL-P group. Plasma GH levels were elevated ( P < 0.05) 2.1-fold in the GRF-P group at 15 min-post-infusion, while GH levels in the GRF-C group were maintained about 70% higher than those in the SAL-P group. Plasma levels of insulin-like growth factor-I (IGF-I) were consistently lower in the GRF-P group at all ages. There were no significant differences in plasma levels of triiodothyronine (T 3), thyroxine (T 4), insulin, or glucose among treatment groups. This study shows that pulsatile infusion of GRF, designed to enhance plasma GH levels, does not improve growth rate, feed efficiency, or body composition of young broiler chickens.

Metabolic clearance of recombinant human growth hormone in health and chronic renal failure.

Despite the increasing therapeutic use of recombinant human growth hormone (rhGH), its metabolic clearance has not been investigated in detail. To evaluate the kinetics of rhGH as a possible function of GH plasma concentration and glomerular filtration rate (GFR), we investigated the steady state metabolic clearance rate (MCR), disappearance half-life, and apparent volume of distribution of rhGH at low and high physiological as well as supraphysiological plasma GH levels during pharmacological suppression of endogenous GH secretion in human subjects with normal and reduced renal function. GH in plasma and urine was determined by an immunoradiometric assay, and GFR by inulin clearance. In all subjects MCR decreased and plasma half-life increased with increasing plasma GH concentrations (P < 0.001). MCR of rhGH was approximately half in patients with chronic renal failure at each GH level and plasma half-life was increased by 25-50%. Allowing for the linear dependence of MCR on GFR and assuming single-compartment distribution, the estimated renal fraction of total MCR was 25-53 and 4-15% in controls and patients, respectively. Saturation of extrarenal disposal of GH was suggested by an inverse hyperbolic relationship between extrarenal MCR and plasma GH concentrations in all subjects. Fractional GH excretion was up to 1,000-fold higher in patients than in controls. We conclude that MCR of hGH is a function of plasma GH concentrations and GFR. Extrarenal elimination is saturable in the upper physiological range of GH concentrations, whereas renal MCR is independent of plasma GH levels. The kidney handles GH like a microprotein involving glomerular filtration, tubular reabsorption, and urinary excretion.

Effects of hypothyroidism on the growth hormone axis in sheep

This study examined the effect of thyroidectomy (TX) on the GH axis in sheep. The secretion of GH was monitored 10 and 77 days after TX or sham-TX when the effects on plasma GH and prolactin levels of the injection of 0.5 micrograms GH-releasing factor (GRF)/kg and 1 microgram thyrotrophin-releasing hormone (TRH)/kg were also assessed. There were no significant differences in GH pulse amplitude, pulse frequency, inter-pulse interval and GH secreted/h between sham-TX and TX animals at 10 or 77 days after TX. There was no difference in the GH response to GRF injection in sham-TX sheep at any time but in TX sheep the GH response was significantly (P < 0.05) attenuated 10 days after TX. After 77 days the GH response was similar to the response before TX. There was no measurable GH response to injection of TRH in sham-operated or TX sheep at any time. The prolactin response to TRH was not affected by TX or sham-TX. These results suggest that TX in sheep does not affect GH secretion but paradoxically the response to GRF is attenuated in hypothyroid sheep in the short term. TRH causes release of prolactin but not GH in sheep.

The role of growth hormone in regulation of low affinity glucocorticoid-binding sites from male rat liver microsomes.

GH participates in the regulation of the expression of several hepatic proteins, some of which are subject to multihormonal control. We have previously shown the participation of glucocorticoids and thyroid hormones in the regulation of the hepatic low affinity glucocorticoid-binding sites (LAGS). Here, we provide evidence that also implicates GH in the endocrine control of the LAGS through the use of several animal models, all of them having a very low or undetectable plasma GH level: the hypothyroid (TX), the hypophysectomized, and the GH-deficient Lewis-derived dwarf rat. In dwarf rats, the level of LAGS was only 35% of that found in normal Lewis rats. Treatment of these rats with human (h) GH significantly increased the LAGS level in a dose-response manner. In TX rats, hGH treatment provoked a significant increase in the LAGS level (from 0.9 +/- 0.2 to 7.2 +/- 0.8 pmol/mg protein), so that it represented about 65% of the level found in intact animals. In both hypothyroid-adrenalectomized and hypophysectomized rats, the isolated effect of hGH was not as pronounced as in TX or dwarf rats; however, a potentiation of the effect of hGH was observed when this hormone was injected together with corticosterone acetate. On the other hand, when hGH, T3, and corticosterone acetate were given in combination to hypophysectomized rats, hGH and T3 behaved as agonists of the LAGS induction at T3 doses lower than or equal to 0.1 microgram/100 g BW and as antagonists at T3 doses higher than this. When T4 was used instead of T3, this hormone was capable of potentiating the effect of hGH at doses lower than or equal to 1.5 micrograms/100 g BW. From these results we conclude that 1) GH as well as thyroid and glucocorticoid hormones participate in the endocrine regulation of the LAGS; and 2) under physiological conditions, it is conceivable that GH, thyroid hormones, and glucocorticoids act synergistically in the endocrine regulation of the LAGS.

The role of growth hormone in regulation of low affinity glucocorticoid- binding sites from male rat liver microsomes

GH participates in the regulation of the expression of several hepatic proteins, some of which are subject to multihormonal control. We have previously shown the participation of glucocorticoids and thyroid hormones in the regulation of the hepatic low affinity glucocorticoid-binding sites (LAGS). Here, we provide evidence that also implicates GH in the endocrine control of the LAGS through the use of several animal models, all of them having a very low or undetectable plasma GH level: the hypothyroid (TX), the hypophysectomized, and the GH-deficient Lewis-derived dwarf rat. In dwarf rats, the level of LAGS was only 35% of that found in normal Lewis rats. Treatment of these rats with human (h) GH significantly increased the LAGS level in a dose-response manner. In TX rats, hGH treatment provoked a significant increase in the LAGS level (from 0.9 +/- 0.2 to 7.2 +/- 0.8 pmol/mg protein), so that it represented about 65% of the level found in intact animals. In both hypothyroid-adrenalectomized and hypophysectomized rats, the isolated effect of hGH was not as pronounced as in TX or dwarf rats; however, a potentiation of the effect of hGH was observed when this hormone was injected together with corticosterone acetate. On the other hand, when hGH, T3, and corticosterone acetate were given in combination to hypophysectomized rats, hGH and T3 behaved as agonists of the LAGS induction at T3 doses lower than or equal to 0.1 microgram/100 g BW and as antagonists at T3 doses higher than this. When T4 was used instead of T3, this hormone was capable of potentiating the effect of hGH at doses lower than or equal to 1.5 micrograms/100 g BW. From these results we conclude that 1) GH as well as thyroid and glucocorticoid hormones participate in the endocrine regulation of the LAGS; and 2) under physiological conditions, it is conceivable that GH, thyroid hormones, and glucocorticoids act synergistically in the endocrine regulation of the LAGS.

Effects of growth hormone on growth performance, haematology, metabolites and hormones in iron-deficient veal calves.

Effects of subcutaneous (s.c.) administration of 50 micrograms/kg body weight of recombinant bovine growth hormone (rbGH) or saline were studied for 11 weeks in 40 intact male veal calves supplied 50 mg or 10 mg of iron (Fe)/kg of milk replacer (MR). Feed intake, average daily gain and growth: feed ratio were reduced in Fe-deficient calves, but not significantly influenced by rbGH. Plasma Fe and haemoglobin concentration, red-cell number and packed cell volume were decreased in Fe-deficient calves (P < 0.05) and rbGH further reduced red-cell number in Fe-deficient calves (P < 0.05). The age-dependent increase of total Fe binding capacity was greater in Fe-deficient calves and enhanced by rbGH (P < 0.05). Plasma urea concentrations increased, whereas glucose (G) and triiodothyronine (T3) levels decreased in Fe-deficient calves. rbGH significantly increased G in calves fed MR containing 50 mg/kg (P < 0.05) and influenced urea concentrations (P < 0.05). Plasma insulin (I) and IGF-I concentrations were lower in Fe-deficient calves (P < 0.05). Plasma GH in the first hours after rbGH injections increased (P < 0.05) to higher levels in calves fed 10 than in those fed 50 mg Fe/kg MR, but incremental changes were comparable. In conclusion, low Fe intake caused haematologic, metabolic and endocrine changes. Plasma IGF-I, I and T3 concentrations after rbGH administration and effects of rbGH on IGF-I in Fe-deficient calves were reduced, even though plasma GH levels were increased.

Progestin-induced growth hormone excess in the dog originates in the mammary gland.

In the dog endogenous progesterone and synthetic progestins may incite overproduction of GH, resulting in acromegaly and insulin resistance. This progrestin-induced excessive GH secretion is characterized by disappearance of the pulsatile secretion pattern and insensitivity to both stimulation with GHRH and inhibition with a somatostatin analog. This progestin-induced GH hypersecretion is not associated with neoplastic transformation at the pituitary level. These observations were the impetus for a search of a possible extrapituitary site of GH production. In four ovariohysterectomized dogs elevated plasma GH levels (46.5 +/- 7.7 micrograms/liter; mean +/- SEM) were induced by administration of synthetic progestins. In these dogs hypophysectomy did not led to a significant decrease in plasma GH levels. Analysis of the GH content of various tissue homogenates revealed that the highest GH immunoreactivity was found in extracts of the mammary gland. Ectopic production of GH in the mammary gland was confirmed by lowering of plasma GH concentration to values within the reference range within 2 h after complete mammectomy in two dogs with progestin-induced elevations of plasma GH levels. In one of these dogs the arterial and elevations of plasma GH levels. In one of these dogs the arterial and venous GH concentrations across the mammary gland were measured and an arterio-venous GH gradient was demonstrated. Displacement studies in the RIA and analysis by reversed-phase HPLC revealed that mammary-derived GH is highly similar to pituitary-derived GH. Immuno-histochemical staining revealed that GH immunoreactivity was localized in focal areas of hyperplastic ductular epithelium. In mammary tissue of healthy untreated female dogs no GH immunoreactivity was found. It is concluded that treatment of dogs with synthetic progestins can induce the overproduction of GH in the mammary gland. This GH is biologically active, highly similar to pituitary derived GH, and originates from foci of hyperplastic ductular epithelium of the mammary gland.