Donal C. Parker

Persistence of rhythmic human growth hormone release during sleep in fasted and nonisocalorically fed normal subjects

Abstract The effects of nonisocaloric feeding and fasting on rhythmic release of HGH in sleep were examined in three normal women. Each was studied on two nights during a base-line-isocaloric period, on the second and third nights of an 80-hr fast, and on the third and sixth nights of a 600-g CHO, 4000-calorie diet. Plasma HGH, insulin, and glucose were determined at 20-min intervals and NEFA at hourly intervals during polygraphically monitored sleep. Normal repetitive patterns of HGH release in sleep occurred in all three subjects during base-line and high-CHO diet periods. No suppression of release occurred in any subject during the 6 days of excessive caloric intake and weight gain of 2.8–3.5% above mean basal weight. Fasting resulted in increased peak HGH concentrations in sleep, but each subject continued her same pattern of release, frequency of peaks, and sequential damping of release during sleep, as did a fourth male subject during a 60-hr fast. HGH release in sleep in fasting exhibited amplification of the normal rhythm. This occurred despite a significant glucose fall to below normal range, undetectable insulins, elevated NEFAs, and weight losses of 4.6–9.4%. NEFA fell sharply at sleep onset on 5 of 6 fast nights suggesting an adrenergic mechanism had been altered at entry into sleep. No pattern of rise in glucose or NEFA comparable to classic HGH effects on substrate followed the early sleep HGH peak in any study period. The data suggest that sleep release of HGH is a primary neural rhythm relatively independent of substrate concentration. Neuronal adaption to utilization of nonglucose substrates in fasting may lead to enhanced rhythmic activity and increased amplitude of the HGH release rhythm in sleep.

Naloxone effects on serum growth hormone and prolactin in man.

Endogenous and exogenous opiate-like compounds have been found to cause increased serum growth hormone and prolactin levels in animals, and, in some cases, humans. Naloxone, a relatively specific narcotic antagonist, decreases serum prolactin and growth hormone levels in animals. Naloxone (20 mg IV) did not significantly alter serum prolactin levels and, minimally but not significantly, increased growth hormone levels in humans to whom it was administered.

Brain Cholinergic Systems and the Pathogenesis of Affective Disorders

Extreme and debilitating fluctuations in mood have long been thought to involve chemical imbalances in the central nervous system. The role of catecholamines in the affective disorders has been emphasized since the pioneering work by Schildkraut and Kety (1967) and others, who noted that drugs which elevate mood and which are effective in the treatment of depression facilitate catecholaminergic transmission in the brain, and conversely, that drugs which may produce depression and that are used in the treatment of manic behavior tend to antagonize the synaptic actions of dopamine and norepinephrine. Measurements of catecholamine metabolites in the urine and cerebrospinal fluid of manic and depressed patients have also produced some evidence consistent with the view that depression is associated with reduced catecholaminergic synaptic transmission (Schildkraut, 1973; Schildkraut and Kety, 1967).

Comparison of oral and intravenous methylphenidate

Oral methylphenidate (1.0 mg/kg) and intravenous methylphenidate (0.5 mg/kg) were compared as to their ability to increase behavioral activation, pulse, blood pressure, and serum growth hormone. Intravenous methylphenidate was considerably more effective than oral methylphenidate in activating behavior and in increasing pulse and blood pressure. Although oral methylphenidate appeared to increase behavioral activation, this effect was not statistically significant.

Methylphenidate and serum prolactin in man

Methylphenidate induces psychostimulation and increases cardiovascular parameters, and its psychostimulant effects have been proposed to occur via a dopaminergic mechanism. The effect of methylphenidate on serum prolactin was utilized as a method of evaluating methylphenidates central dopaminergic effects. Methylphenidate was not found to exhibit a consistent effect on serum prolactin. Thus, its effect on serum prolactin does not parallel its behavioral activating properties, suggesting that such activation may not involve dopamine. Possibly, norepinephrine or other noncatecholaminergic neurotransmitters are involved in methylphenidate-induced behavioral activation.

Sleep Release of Human Growth Hormone in Treated Juvenile Diabetics: Similarity to Normal Subjects and Nonsuppression by Hyperglycemia

The effect of diabetic nocturnal hyperglycemia upon HGH release in sleep was studied in five insulin-treated, stable, nonobese juvenile diabetics on eleven nights and compared to mean release in thirteen normal young men. All were studied by sleep polygraphy. Samples were drawn every twenty minutes from indwelling venous catheters without disturbing sleep. HGH was measured by RIA and plasma glucose concentration by O-toluidine. Despite hyperglycemia of 195-382 mg. per 100 ml. on nine out of eleven nights at the time of sleep HGH peak, the repetitive nightly pattern of HGH release in diabetics resembled those of normals. The diabetic groups mean HGH concentration during sleep was 4.0 ± 0.6 ng./ml. (± S.E.) and mean peak sleep HGH concentration was 11.2 ±: 1.3 ng./ml., which were not signicantly different from those of normals (3.4 ± 0.3 and 12.5 ± 1.4 ng./ml. ± S.E. respectively). Thus, diabetic hyperglycemia, similar to constant glucose infusion hyperglycemia in normals, does not result in suppression of HGH release in sleep. This indicates that hyperglycemia is not an important regulator of rhythmical HGH release in sleep and suggests a primary neural character of this rhythm. HGH release in sleep was not enhanced in treated juvenile diabetes.

Biological effect of bright light

1. Five minute bright light exposures reduced plasma levels of melatonin in eight normal subjects. 2. No significant change in ACTH levels occurred. 3. These results raise the possibility that short intense light exposures can synchronize circadian rhythms as well as benefit patients with seasonal affective disorder. They also indicate that short pulses of bright light do not affect pituitary ACTH production.

PHYSOSTIGMINE RESPONSES AS MARKERS IN AFFECTIVE DISORDER PATIENTS

Converging lines of evidence from a variety of independent research studies suggest that affective disorder patients may be more reactive to centrally acting cholinomimetic agents. To explore this possibility, the current study compared the behavioral and neuroendocrine effects of the cholinesterase inhibitor, physostigmine salicylate (.022 mg/kg), in affective and non–affective disorder psychiatric patients. Affective disorder patients were found to have a relatively greater tendency to develop behavioral inhibition and anergia, negative affect and exaggerated prolactin responses following physostigmine infusion. No significant differences were found with respect to physostigmine-induced increases in pulse, blood pressure or serum cortisol. Thus, it is possible that exaggerated behavioral and prolactin responses to physostigmine may be markers of affective disorder.

METHYLPHENIDATE INDUCED CHANGES IN BEHAVIOR, GROWTH HORMONE, AND PROLACTIN

ABSTRACT Intravenous methylphenidate (0.5 mg/kg) caused human serum growth hormone to be significantly increased following methylphenidate infusion, an effect attenuated in schizophrenics, as contrasted to non-psychotic patients, and in antipsychotic drug treated individuals. Serum prolactin levels significantly decreased from baseline after methylphenidate infusion.