Leptin Prevents Fasting-Mediated Reductions in Pulsatile Secretion of Luteinizing Hormone and Enhances Its Gonadotropin-Releasing Hormone-Mediated Release in Heifers1

Abstract

We tested the hypothesis that leptin could prevent fasting-mediated reductions in pulsatile secretion and modify GnRH-mediated release of LH in heifers approaching puberty. Thirteen crossbred, prepubertal heifers (13.5-16 mo; 280-350 kg) exhibiting frequencies of pulses of LH between 0.67 and 1 pulse/h, were assigned randomly to two groups: 1). control (n = 6), fasted for 72 h with s.c. injections of saline at 12-h intervals, and 2). leptin (n = 7), fasted for 72 h with s.c. injections of oleptin (19.2 microg/kg) at 12-h intervals. Blood samples were collected intensively for 6 h on Days 0 and 3. This was followed on Day 3 with sequential administration of physiological (0.0011 microg/kg, i.v.) and pharmacological (0.22 microg/kg, i.v.) doses of GnRH and additional blood sampling. Leptin treatment increased (P = 0.0003) plasma concentrations of leptin 5-6-fold compared to controls. Fasting caused a marked decline (P = 0.01) between Days 0 and 3 in the frequency of LH pulses in controls; however, this effect was prevented in the leptin group, with pulse frequency increasing (P < 0.008) from Day 0 to 3. Leptin treatment increased GnRH-induced release of LH at both low (P = 0.04) and high (P = 0.02) doses. Plasma insulin and insulin-like growth factor-1 were reduced by fasting and unaffected by leptin. Leptin increased mean concentrations of growth hormone. Results indicate, for the first time, that exogenous leptin can prevent fasting-mediated reductions in the frequency of LH pulses and modify GnRH-mediated release of LH in intact, prepubertal heifers.

Fasting and Glucose Effects on Pituitary Leptin Expression

“…This agrees with most previous studies of fasted or fooddeprived animals that found reductions in serum leptin; however, they tested periods longer than 24 hr (Ahima et al 1996;Casanueva and Dieguez 1999;Dallman et al 1999;Schneider and Zhou 1999;Schneider et al 2000Schneider et al ,2002Maciel et al 2004;Luque et al 2007). Fasting-mediated reductions in serum leptin after 24 hr …”

Pituitary Leptin-A Paracrine Regulator of Gonadotropes: A Review

“…This points to independent regulators for pituitary leptin and our studies show that they include estrogen and GHRH [98] and GnRH [93], all of which would be reduced in a fasted state [20,58,67,68,76,78,186,187]. NPY would not be reduced, however receptors for this neuropeptide would likely be reduced because of the requirement for estrogen, at least in female rats.…”

Role of Leptin in the Reproduction and Metabolism: Focus on Regulation by Seasonality in Animals

“…Moreover, treatment with exogenous leptin prevented these decreases, implying a direct action of leptin at the hypothalamic level (Maciel et al, 2004a). In contrast, mature cows subjected to similar feeding restrictions, resulting in analogous metabolic responses to those seen peripubertal heifers (e.g., decreased leptin mRNA expression in adipose tissue, decreased plasma concentrations of leptin, insulin and IGF-1), did not exhibit a decrease in the pulsatile secretion of LH (Maciel et al, 2004b). However, similar to the heifers, mature cows subjected to short-term fasting became intensely hypersensitive to exogenous leptin.…”