The obese gene (OB) product, leptin, has been shown to exert control on metabolic processes such as food intake and body weight homeostasis, possibly through a neuropeptide Y (NPY) neurotransmission. More recently, leptin has been shown to control several neuroendocrine axes, modulating pituitary hormone secretions in function of metabolic conditions. Since in the rat growth hormone (GH) secretion is dependent upon prevailing metabolic conditions, and NPY has been shown to be implicated in the feedback mechanisms of this hormone, we reasoned that leptin could also exert control over GH secretion and we examined this hypothesis in male rats submitted to a 3-day fast. Circulating leptin concentrations measured by RIA abruptly fell to low values after 24 h of fasting and remained low thereafter. Upon refeeding, leptin secretion regularly increased. As shown by others, pulsatile GH secretion had disappeared after 3 days of fasting. Centrally administered leptin (10 µg/day, i.c.v. infusion initiated at the beginning of the fasting period) totally prevented the disappearance of pulsatile GH secretion. No leak of centrally administered leptin to the general circulation was observed. Infusing the same amount of leptin intracerebroventricularly to rats receiving ad libitum feeding produced a severe reduction in food intake but maintained a normal GH secretory pattern. In contrast, pair-fed rats, submitted to the same food restriction, exhibited a marked reduction in GH secretion. Hypothalamic NPY gene expression, estimated by Northern blot analysis, was significantly increased in fasting rats, and decreased in leptin-treated, fasting rats. In rats receiving ad libitum feeding, leptin treatment reduced NPY gene expression, consistent with the observed reduction in food intake, whereas pair-fed animals logically exhibited increased NPY gene expression. In both situations with reduced feeding, normal GH secretion was seen in leptin-treated animals exhibiting low NPY gene expression, whereas decreased or abolished GH secretion was seen in animals not receiving leptin and exhibiting increased NPY mRNA levels. Interestingly, despite maintenance of normal GH secretion in leptin-treated, fasting rats, plasma IGF-I levels were low, as in vehicle-treated rats. Indeed, hepatic gene expression for both GH receptor and IGF-I was markedly reduced by fasting, and no correction was seen with leptin treatment. In summary, the regulation of GH secretion, at least the changes linked with malnutrition, appears to be dependent upon a leptin signal, perceived centrally, possibly related to circulating levels of this new hormone. The present data suggest that leptin can rescue normal pulsatile GH secretion by preventing the documented inhibitory action of NPY on GH secretion.

No abstract

The ability of hCG and LH to induce testosterone (T) secretion by Leydig cells is well documented. However, the influence of the pulsatile nature of LH secretion, with varying frequency and amplitude, on T production in vivo is less clear. In our earlier studies on the relationship between pulsatile LH release and T secretion in adult male rats, no simple causality was observed. The recent availability of rat recombinant (rec) LH prompted us to study the effects of one and of three i.v. pulses of different doses of rat recLH on T secretion in adult male rats rendered hypogonadotropic by treatment with the GnRH antagonist cetrorelix. One or three supraphysiological pulses of 1.0 microg of rat recLH produced similar maximal T responses. In contrast, high physiological LH pulses (0.1 microg) produced discrete T-response peaks, whereas multiple low pulses of LH (0.03 microg) were needed before a T response was achieved. The T stimulation was greatly diminished after an LH pulse of 0.1 microg if rats had been treated on the previous day with pulses of 0.03 vs. 0.1 microg rat recLH, apparently because of prolonged LH deprivation and lack of Leydig cell priming due to the GnRH antagonist treatment. The novel preparation of rat recLH provides a physiologically relevant tool for studying the complex relationship between pulsatile LH release and T secretion in male rats.