Growth Hormone Regulation by Melatonin and Serotonin

Abstract

THERE is evidence to suggest the existence of a pineal gland substance which moderates growth both in man and the rat. In man, non-parenchymal tumours, such as gliomas or teratomas which result in destructive lesions of the pineal gland, are associated with precocious puberty^1,2 and it has been hypothesized that such lesions prevent the pineal from secreting gonadal² and growth^3,4 inhibitory factors. It was recently reported⁵ that the ability of the pineal gland to influence both growth and gonadal development may be due to two distinct physiological mechanisms. Rats which are blinded or kept in constant darkness show reduced body weight^4,5, reduced tibeal length⁴, and reduced accessory organ weights⁴ as well as retarded puberty^2,5,6. Blinded rats were also found⁴ to have significantly reduced pituitary gland stores of growth hormone. The effects of blinding or constant darkness on growth and growth hormone stores were abolished by pinealectomy^4,7—a procedure also found⁸ to increase the gain of body weight in otherwise normal rats. Pinealectomy has also been reported to result in increased growth of experimental tumours in rats⁹. The observation¹⁰ of a diurnal fluctuation in the secretion of growth hormone in the rat further suggests that the lighting regime can modify this release. When lighting is reduced, concentrations of the pineal hormone melatonin (N-acetyl-o-methylserotonin) are increased because it is synthesized within the pineal gland from serotonin (5-hydroxytryptamine) by the action of the enzymes serotonin-N-acetyltransferase and hydroxyindole-o-methyltransferase, both of which exhibit their highest activities in the absence of light^11,12. The fact that the conditions favouring high melatonin production correlate with those which cause reduced growth (and the other way round) suggests that melatonin has an inhibitory role in growth hormone secretory mechanisms. Collu et al.¹³ demonstrated that intraventricular injections of serotonin stimulate secretion of growth hormone in the rat, and they proposed that in this animal secretion of growth hormone is controlled through serotoninergic pathways. Serotonin has also been implicated as the stimulus for secretion of growth hormone after the onset of slow-wave (non-rapid eye movement, NREM) sleep in normal humans¹⁴. It thus seems that serotonin and its pineal derivative, melatonin, may have opposing effects on the secretion of growth hormone. We describe here experiments which support this contention.