The effect of recombinant IGF-I on anterior pituitary function in healthy volunteers

OBJECTIVE Insulin-like growth factor-I is the mediator of many of the actions of GH and is a potent metabolic regulator. Recombinant IGF-I (rhIGF-I) is of potential value in the treatment of syndromes associated with either GH or insulin resistance. This study was designed to assess the effects of subcutaneous (s.c.) rhIGF-I on anterior pituitary function. DESIGN Double-blind, placebo controlled, randomized cross-over study. The interval between investigations was 2 weeks. SUBJECTS Twelve normal volunteers received on one occasion a single S.C. dose of 40 μg/kg rhIGF-I and on the other, placebo. MEASUREMENTS Circulating levels were measured, over 24 hours, of GH, LH, FSH, PRL, TSH, cortisol, ACTH, glucose, IGF-I, IGF-II, Insulin, C-peptide; IGF binding proteins by Western ligand blotting; total IGF bioactivity using FRTL-5 thyroid cells; and glucose by the glucose oxidase method. RESULTS Recombinant IGF-I Increased AUC for plasma IGF-I, measured by radioimmunoassay (rhIGF-I mean 7065 ± SEM 33 vs 3895 ± 204 μg/l, P < 0·0001) and IGF bioactivity (22·5 ± 3·4 vs 14·2 ± 1·8 U/ml, P < 0·001) but plasma IGF-II fell (9308 ± 403 vs 11052 ± 451 μg/l, P < 0·0001). There was no biochemical or clinical evidence of hypoglycaemia and no difference in mean glucose levels. No difference existed in AUC for GH, LH, FSH, ACTH and cortisol between rhIGF-I and placebo; additionally, pulse number and amplitude for GH and LH were unaffected. TSH fell following rhIGF-I (33·0 ± 3·36 vs 42·5 ± 5·98 mU h/l, P= 0·01). Both mean plasma C-peptlde (0·73 ± 0 06 vs 0·91 ± 0±05 nmol/l, P= 0·03), and insulin (10·81 ± 1·02 vs 15·36 ± 1·18 mU/l, P= 0·03) were lower following rhIGF-I. There was no change In IGFBPs. CONCLUSION A single injection of 40 μg/kg of subcutaneous rhIGF-I does not cause hypoglycaemia. IGF bioactivity was increased without inhibition of GH secretion. The only change observed in anterior pituitary function was a fall in plasma TSH.     

The effect of stressful diagnostic studies and surgery on anterior pituitary hormone release in man

The hormonal response of the anterior pituitary was studied in 10 normal males undergoing treadmill exercise testing, in 5 male patients undergoing diagnostic gastroscopy, and in 8 male patients undergoing elective surgery under general anaesthesia. Serum TSH was depressed below the baseline value at 2 and 3 h post-treadmill exercise, at 1, 2 and 3 h post-gastroscopy and from 10 min through 2 h post-surgery. Serum triiodothyronine was depressed below the baseline value at 10 min through 2 h post-surgery. Serum prolactin, growth hormone and cortisol were elevated by all three stressful procedures. Both gastroscopy and surgery resulted in an elevation of serum luteinizing hormone levels. There was no significant change in serum FSH levels in any of the three procedures. The post-stress depression in TSH levels could result from the suppressive effect at the hypothalamic-pituitary level of high serum levels of cortisol generated by the stress of the procedures.     

The effect of short-term glucagon infusion on kidney function in normal man

Summary Kidney function was studied in six normal males before and during a 2 h glucagon (10 ng/kg/min) infusion. The following variables were determined during each 20 min clearance period; glomerular filtration rate (GFR), renal plasma-flow (RPF), filtration fraction (FF), urinary albumin and ₂-microglobulin-excretion rates. Glucagon infusion resulted in a fourfold increase in plasma glucagon concentration. The infusion induced a significant increase in GFR (+9%), FF (+ 9%) and urinary ₂-microglobulin excretion rate (+ 32%), (p<0.01). RPF and urinary albumin excretion rates were not significantly changed. We suggest that glucagon may contribute to the reversible kidney function alterations typically found in poorly regulated juvenile diabetes, a state with relative or absolute hyperglucagonaemia.     

Lack of indomethacin effect on thyroid function in man

Administration of indomethacin 200 mg daily for 2 days to four euthyroid volunteers was without significant effect on serum triiodothyronine or thyroxine and caused no cinsistent alteration of serum TSH. There were minor and variable changes in the pattern of thyroidal iodine release (TIR) in these euthyroid subjects. In one subject both the TIR pattern and serum TSH concentration were altered in the same direction, suggesting that these minor changes were of central origin. Indomethacin also had no effect on the stimulated pattern of TIR in one euthyroid subject receiving daily exogenous TSH injections, or in a patient with untreated hyperthyroid Graves' disease. Prostaglandin A1 infusion in one subject did not alter serum TSH or thyroidal iodine release. It is concluded that prostaglandins probably have no obligatory physiological role in modulating TSH or thyroid hormone secretion in man.     

The effect of diazepam on human gastric secretion

Human basal gastric secretion is markedly reduced after oral administration of 10 mg diazepam. This effect lasts for five hours.

Gastric nocturnal secretion, collected five hours after the last meal, reveals a decline towards the morning hours with an average of 25% in placebo-treated patients. A comparison between placebo and diazepam reveals a significantly greater decrease of 47% in volume after giving parenterally 10 mg diazepam without noticeable side effects.

     

Famotidine has no significant effect on gonadal function in man

The effect of a single bedtime dose of famotidine 40 mg on gonadal function was studied in 8 male duodenal ulcer patients. The drug was orally administered for 4 weeks. Our results show that this new H2 blocker influences basal and stimulated serum levels of neither testosterone nor gonadotrophins (LH, FSH). Besides, no significant variations were observed before and after famotidine treatment in seminal fluid characteristics evaluated in 5 out of 8 cases. It can be concluded that famotidine appears to leave gonadal function unaffected in man.     

The effect of selective dopamine-1 receptor stimulation on renal and adrenal function in man

We studied the actions of iv fenoldopam, a selective dopamine-1 (DA-1) receptor agonist, in 10 normal men eating a diet containing 150 meq sodium and 60 meq potassium per day. During DA-1 receptor stimulation systemic hemodynamic function did not change. Fenoldopam resulted in an increase in urine flow rate from 13 +/- 1 (+/- SE) to a peak of 17 +/- 2 mL/min (P less than 0.05) and an increase in renal plasma flow from 344 +/- 39 to 481 +/- 44 mL/min (P less than 0.05). Urinary sodium excretion and fractional excretion of sodium both increased. Urinary sodium excretion rose to a maximum of 0.32 +/- 0.05 compared with a control value of 0.21 +/- 0.03 meq/min (P less than 0.01), while fractional excretion of sodium rose to 2.7 +/- 0.6 compared with a control value of 1.6 +/- 0.1% (P less than 0.05). The glomerular filtration rate did not change. Administration of a predominantly DA-2 antagonist during continuous DA-1 receptor stimulation did not block the fenoldopam-induced natriuresis. The rise in plasma aldosterone concentration after metoclopramide administration was blunted by DA-1 receptor activation [19.2 +/- 2.9 during control compared with 12.7 +/- 1.3 ng/dL (P less than 0.01) during fenoldopam]. No change occurred in serum potassium, plasma cortisol, or PRA. We conclude that selective DA-1 receptor stimulation in man produces sustained natriuresis and inhibition of aldosterone release by direct renal and adrenal effects.