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Leptin’s Actions on the Reproductive Axis: MECHANISMS OF LEPTIN’S ACTIONS ON REPRODUCTION(5)

REPRODUCTION(5)

Thus the potential exists for leptin to influence reproductive function during fasting through altering the availability of POMC gene products. Indeed, the endogenous opioid p-endorphin as well as a-melanocyte-stimulating hormone (a-MSH) have been implicated in modulating both feeding and reproduction. If leptin-induced changes in р-endorphin transmission influence GnRH secretion, it may be through indirect means, as GnRH neurons are believed to lack the classical opioid receptor subtypes (^, к, and 8). Leptin’s inhibitory actions on food intake are thought to be due, in part, to signaling through hypothalamic melanocortin type 4 (MC4) receptors, for which a-MSH (among other POMC gene products) is an endogenous ligand. However, experiments demonstrating the involvement of MC4 receptors in transducing leptin’s stimulatory effects on reproductive parameters using specific MC4 agonists/antagonists have not yet been published. ampicillin antibiotic

The orexigenic peptide neuropeptide Y (NPY) is another substance found in the Arc that plays a dual role in feeding and reproduction. NPY has been shown to stimulate GnRH release, an action that may be mediated in vivo by synaptic contacts between NPY- and GnRH-containing neurons. NPY mRNA levels in the Arc are elevated in both fasted and leptin-deficient animals; this increase is believed to be the cause, in part, of the hyperpha-gia and subsequent obesity in ob/ob mice. NPY mRNA-containing neurons in the Arc also express Ob-R mRNA, suggesting the possibility that NPY mRNA levels are directly responsive to circulating leptin. Although evidence exists for stimulatory effects of NPY on GnRH/LH secretion when given acutely, NPY appears to act in an inhibitory fashion when delivered chronically or to animals with low estrogen levels. However, overexpression of NPY alone cannot account for the reproductive failure of the ob/ob mouse, since mice that carry both the ob/ob genotype and a homozygous null mutation for NPY have only a partial restoration of fertility.