Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system  Erdal Budak, M.D., Manuel Fernández Sánchez, M.D., José Bellver, M.D., Ana Cerveró, Ph.D., Carlos Simón, M.D., Antonio Pellicer, M.D.  Fertility and Sterility  Volume 85, Issue 6, Pages 1563-1581 (June 2006) DOI: 10.1016/j.fertnstert.2005.09.065 Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 1 Two opposing sets of neuronal activity that control appetite are present in the ARC of the hypothalamus: the appetite-stimulating circuit and the appetite-inhibiting circuit. The two circuits send signals mainly to the PVN to modulate feeding behavior and energy expenditure. Peripheral hormones such as insulin, leptin, ghrelin, and PYY3-36 cross the blood–brain barrier and exert various effects on this system. Likewise, these peripheral hormones also reach the GnRH-secreting neurons within the PVN and ARC, which are in close proximity to theappetite-controlling areas to modulate GnRH pulsatility, consequently affecting FSH and LH production andsecretion from the anterior pituitary gland. NPY = neuropeptide Y; AgRP = agouti-related peptide; CART=cocaine and amphetamine–regulated transcript peptide; POMC = Pro-opiomelanocortin. Budak. Adipose tissue and gut-derived hormones and reproduction. Fertil Steril 2006. Fertility and Sterility 2006 85, 1563-1581DOI: (10.1016/j.fertnstert.2005.09.065) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 2 The appetite-stimulatory circuit produces the neurotransmitters neuropeptide Y (NPY) and agouti-related peptide (AgRP), which up-regulate appetite and promote feeding (right column). Neuropeptide Y directly signals to the PVN, whereas AgRP acts indirectly. The appetite-inhibitory circuit mainly produces α-melanocyte-stimulating hormone (α-MSH), which operates to inhibit appetite and feeding (left column). Increased levels of leptin and insulin stimulate the appetite-inhibitory circuit through up-regulation of α-MSH and inhibit the appetite-stimulatory neuron by suppressing NPY and AgRP mRNA expression in the hypothalamus. In contrast, increased levels of ghrelin stimulate the appetite-stimulatory neurons. Budak. Adipose tissue and gut-derived hormones and reproduction. Fertil Steril 2006. Fertility and Sterility 2006 85, 1563-1581DOI: (10.1016/j.fertnstert.2005.09.065) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions

FIGURE 3 Leptin of endocrine and paracrine origin is present within the uterine cavity environment during the implantation process. Leptin and its receptor are expressed in both the endometrium and the preimplantation embryo (reprinted with the permission from the Endocrine Society). Open diamonds, leptin of endometrial origin; filled circles, leptin of endocrine origin; open circles, leptin of embryonic origin; Y = leptin of receptor. Budak. Adipose tissue and gut-derived hormones and reproduction. Fertil Steril 2006. Fertility and Sterility 2006 85, 1563-1581DOI: (10.1016/j.fertnstert.2005.09.065) Copyright © 2006 American Society for Reproductive Medicine Terms and Conditions