Estrogen and leptin have differential effects on FSH and LH release in female rats

Prior experiments have shown that the adipocyte hormone leptin can advance puberty in mice. We hypothesized that it would also stimulate gonadotrophin secretion in adults. Since the secretion of follicle stimulating hormone ( FSH) and luteinizing hormone (LH) is drastically affected by estrogen, we h ypothesized that leptin might have different actions dependent on the dose of estrogen, Consequently in these experiments, we tested the effect of inj ection of leptin into the third cerebral ventricle of ovariectomized animal s injected with either the oil diluent, 10 mu g or 50 mu g of estradiol ben zoate 72 hr prior to the experiment. The animals were ovariectomized 3-4 we eks prior to implantation of a cannula into the third ventricle 1 week befo re the experiments. The day after implantation of an external jugular cathe ter, blood samples (0.3 ml) were collected just before and every 10 min for 2 hr after 3V injection of 5 mu l of diluent or 10 mu g of leptin, Both do ses of estradiol benzoate equally decreased plasma LH concentrations and pu lse amplitude, but there was a graded decrease in pulse frequency. In contr ast, only the 50-mu g dose of estradiol benzoate significantly decreased me an plasma FSH concentrations without significantly changing other parameter s of FSH release. The number of LH pulses alone and pulses of both hormones together decreased as the dose of estrogen was increased, whereas the numb er of pulses of FSH alone significantly increased with the higher dose of e stradiol benzoate, demonstrating differential control of LH and FSH secreti on by estrogen, consistent with alterations in release of luteinizing hormo ne releasing hormone (LHRH) and the putative FSH-releasing factor (FSHRF), respectively. The effects of intraventricularly injected leptin were drastically altered by increasing doses of estradiol benzoate, There was no significant effect of intraventricular injection of leptin (10 mu g) on the various parameters of either FSH or LH secretion in ovariectomized, oil-injected rats, wherea s in those injected with 10 mu g of estradiol benzoate there was an increas e in the first hr in mean plasma concentration, area under the curve, pulse amplitude, and maximum increase of LH above the starting value (Delta(max) ) on comparison with the results in the diluent-injected animals In which t here was no alteration of these parameters during the 2 hr following inject ion. The pattern of FSH release was opposite to that of LH and had a differ ent time-course. In the diluent-injected animals, probably because of the s tress of injection and frequent blood sampling, there was an initial signif icant decline in plasma FSH at 20 min after injection, followed by a progre ssive increase with a significant elevation above the control values at 110 and 120 min. In the leptin-injected animals, mean plasma FSH was nearly co nstant during the entire experiment, coupled with a significant decrease be low values in diluent-injected rats, beginning at 30 min after injection an d progressing to a maximal difference at 120 min. Area under the curve, pul se amplitude, and Delta(max) of FSH was also decreased in the second hour c ompared to values in diluent-injected rats. In contrast to the stimulatory effects of intraventricular injection of leptin on pulsatile LH release man ifest during the first hour after injection, there was a diametrically oppo site, delayed significant decrease in pulsatile FSH release. This different ial effect of leptin on FSH and LH release was consistent with differential effects of leptin on LHRH and FSHRF release. Finally, the higher dose of E -2 (50 mu g) suppressed release of both FSH and LH, but there was little ef fect of leptin under these conditions, the only effect being a slight (P < 0.04) increase in pulse amplitude of LH in this group of rats. The results indicate that the central effects of leptin on gonadotropin release are str ongly dependent on plasma estradiol levels. These effects are consistent wi th differential effects of estrogen on the release of LHRH and the putative FSHRF.