The possible role of prolactin in the circadian rhythm of leptin secretionin male rats

In humans there is a circadian rhythm of leptin concentrations in plasma wi th a minimum in the early morning and a maximum in the middle of the night. By taking blood samples from adult male rats every 3 hr for 24 hr, we dete rmined that a circadian rhythm of plasma leptin concentrations also occurs in the rat with a peak at 0130h and a minimum at 0730h, To determine if thi s rhythm is controlled by nocturnally released hormones, we evaluated the e ffect of hormones known to be released at night in humans, some of which ar e also known to be released at night in rats. In humans, prolactin (PRL), g rowth hormone (GH), and melatonin are known to be released at night, and ad renocorticotropic hormone (ACTH) release is inhibited, In these experiments , conscious rats were injected intravenously with 0.5 mi diluent or the sub stance to be evaluated just after removal of the first blood sample (0.3 ml ), and additional blood samples (0.3 ml) were drawn every 10 min thereafter for 2 hr. The injection of highly purified sheep PRL (500 mu g) produced a rapid increase in plasma leptin that persisted for the duration of the exp eriment. Lower doses were ineffective. To determine the effect of blockade of PRL secretion on leptin secretion, alpha bromoergocryptine (1.5 mg), a d opamine-2-receptor agonist that rapidly inhibits PRL release, was injected. It produced a rapid decline in plasma leptin within 10 min, and the declin e persisted for 120 min. The minimal effective dose of GH to lower plasma l eptin was 1 mg/rat. Insulin-like growth factor (IGF-1) (10 mu g), but not I GF-2 (10 mu g), also significantly decreased plasma leptin. Melatonin, know n to be nocturnally released in humans and rats, was injected at a dose of 1 mg/rat during daytime (1100h) or nighttime (2300h). It did not alter lept in release significantly. Dexamethasone (DEX), a potent glucocorticoid, was ineffective at a 0.1-mg dose but produced a delayed, significant increase in leptin, manifest 100-120 min after injection of a 1 mg dose. Since gluco corticoids decrease at night in humans at the time of the maximum plasma co ncentrations of leptin, we hypothesize that this increase in leptin from a relatively high dose of DEX would mimic the response to the release of cort icosterone following stress in the rat and that glucocorticoids are not res ponsible for the circadian rhythm of leptin concentration. Therefore, we co nclude that an increase in PRL secretion during the night may be responsibl e, at least in part, for the nocturnal elevation of leptin concentrations o bserved in rats and humans.