Regulation of somatotroph cell function by the adipose tissue

Abstract

Obese subjects exhibit a marked decrease in plasma growth hormone (GH) levels. However, the mechanisms by which increased adiposity leads to an impairment of GH secretion are poorly understood. Recent evidence suggests that the adipose tissue can markedly in¯uence GH secretion via two different signals, namely free fatty acids (FFA) and leptin. FFA appear to inhibit GH secretion mainly by acting directly at pituitary level. Interestingly, reduction in circulating FFA levels in obese subjects led to a marked increase in GH responses to different GH secretagogues. This indicates that FFA exert a tonic inhibitory effect that contributes to blunted GH secretion in obese subjects. Recent data have shown that leptin is a metabolic signal that regulates GH secretion, since the administration of leptin antiserum to adult rats led to a marked decrease in spontaneous GH secretion. However, leptin prevents,the inhibitory effect exerted by fasting on plasma GH levels. The effect of leptin in adult rats appears to be exerted at hypothalamic level by regulating growth hormone releasing hormone (GHRH), somatostatin and neuropeptide Y (NPY)-producing neurones. In addition, during fetal life or following the development of pituitary tumors, leptin can also act directly at the anterior pituitary.

Effects of 36 hour fasting on GH/IGF-I axis and metabolic parameters in patients with simple obesity. Comparison with normal subjects and hypopituitary patients with severe GH deficiency

“…8,30,34 Stimulatory role of leptin in the regulation of rat somatotroph function has been shown; in fact, fasting inhibits GH secretion and leptin restores it. 9,11 However, in humans fasting stimulates GH while inhibiting leptin levels 31 and the fasting-induced leptin decrease is more marked in normal than in obese subjects. 35 Thus, the lack of GH response to fasting in obesity is unlikely to reflect leptinmediated mechanism.…”

“…The chronic elevation of circulating FFA levels, which were further enhanced by fasting, could also have a key role in counteracting the GH response to starvation in obesity. 10,11,29 FFA has a strong inhibitory action on somatotroph secretion acting at either the pituitary or the hypothalamic level; 31,32,36 in fact, lipolysis inhibitors restore GH secretion in obesity. 10,11,29,37 In the absence of any significant increase in GH secretion obese patients in our study showed normal activation of lipolysis; this probably reflects the fasting-induced response of other contraregulatory hormones.…”

“…10,11,29 FFA has a strong inhibitory action on somatotroph secretion acting at either the pituitary or the hypothalamic level; 31,32,36 in fact, lipolysis inhibitors restore GH secretion in obesity. 10,11,29,37 In the absence of any significant increase in GH secretion obese patients in our study showed normal activation of lipolysis; this probably reflects the fasting-induced response of other contraregulatory hormones. 38 In this context, modification in IGF-I bioactivity brought about by fasting-induced changes in the most important binding proteins could play a major metabolic role.…”

“…5,6 Recent evidence favors the hypothesis for abnormalities in peripheral hormones and metabolic factors such as enhanced negative free insulin growth factor-I (IGF-I) feedback, 7 hyperinsulinism, 8 alterations in leptin activity 9 and elevated free fatty acids (FFA). 10,11 Fasting strikingly stimulates somatotroph secretion in normal healthy humans; 12,13 reduction in the negative IGF-I feedback action as well as CNS-mediated mechanisms such as concomitant reduction in somatostatin activity and GHRH hyperactivity are likely to play major role. 14,15 Somatotroph insufficiency in obesity is reversible after long-term diet-induced weight loss, 16 but the effect of fasting is still controversial.…”

The influence of physical exercise on alterations in concentrations of neuropeptide Y, leptin and other selected hormonal and metabolic parameters in sportspeople

“…NPY inhibits GH secretion, [36], but leptin, in physiological conditions, by inhibiting somatostatin release and stimulating GHRH (Growth hormone releasing hormone) secretion, stimulates GH [2]. Excess of growth hormone decreases leptin blood concentration [3].…”