Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroendocrine and behavioral responses to stress, including stressinduced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress. In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased ''free'' CRH and͞or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in maintaining appropriate levels of these peptides in the central nervous system.Corticotropin-releasing hormone (CRH) is the key mediator of the mammalian endocrine, behavioral, autonomic, and immune responses to stress (1). Within the hypothalamicpituitary-adrenal (HPA) axis, CRH is the principal regulator of pituitary adrenocorticotropic hormone (ACTH) and adrenal glucocorticoid secretion in response to stressful stimuli. Within the central nervous system (CNS), CRH acts as a neurotransmitter to elicit anxiogenic-like effects, decrease food intake, reduce weight gain, modulate locomotor activity, and improve arousal and learning (2-4). Aberrant CRH activity has been implicated in the pathophysiology of a variety of human psychiatric disorders, including major depression, anxiety disorders, and anorexia (1, 5).The actions of CRH in the CNS and pituitary are mediated via binding to two distinct CRH receptors, CRH-R1 and CRH-R2 (6). CRH also is bound by CRH-binding protein (CRH-BP), a 37-kDa protein that binds CRH with an affinity equal to or greater than the CRH-Rs (7-9). CRH-BP mRNA is expressed exclusively in the brain and pituitary of rodents, whereas it is detected in human brain, pituitary, liver, and placenta (9-11). Major CNS sites of CRH-BP mRNA expression in rodents are cerebral cortex, amygdala, bed nucleus of the stria terminalis, raphe nuclei, brainstem reticular formation, and olfactory, auditory, trigeminal and vestibular sensory relay systems (10). These sites of CRH-BP expression include several examples of cellular colocalization with CRHproducing neurons (i.e., lateral septal nucleus, bed nucleus of the stria terminalis, medial preoptic area, central nucleus of the amygdala) or CRH target cells, including anterior pituitary corticotropes that express CRH-R1 (10).Both CRH-BP and CRH-R2 mRNA are present in lateral septum, a site of expression of both CRH and urocortin (12). Uroco...

Corticotropin-releasing hormone (CRH) is the primary hypothalamic releasing factor that mediates the mammalian stress response. The CRH-binding protein (CRH-BP) is secreted from corticotropes, the pituitary CRH target cells, suggesting that the CRH-BP may modulate hypothalamic-pituitary-adrenal (HPA) axis activity by preventing CRH receptor stimulation. Transgenic mice were generated that constitutively express elevated levels of CRH-BP in the anterior pituitary gland. RNA and protein analyses confirmed the elevation of pituitary CRH-BP. Basal plasma concentrations of corticosterone and adrenocorticotropin hormone (ACTH) are unchanged, and a normal pattern of increased corticosterone and ACTH was observed after restraint stress. However, CRH and vasopressin (AVP) mRNA levels in the transgenic mice are increased by 82 and 35%, respectively, to compensate for the excess CRH-BP, consistent with the idea that CRH-BP levels are important for homeostasis. The transgenic mice exhibit increased activity in standard behavioral tests, and an altered circadian pattern of food intake which may be due to transgene expression in the brain. Alterations in CRH and AVP in response to elevated pituitary CRH-BP clearly demonstrate that regulation of CRH-BP is important in the function of the HPA axis.

E2 priming seems to improve hypothalamic-pituitary-ovarian axis function and systemic inflammation in ovulatory, obese women. Reducing chronic inflammation at the pituitary level may decrease the burden of obesity on fertility.

This prospective, cross-sectional study of 60 women compares self- reported height, weight, and BMI with measured values. Self-reported BMI (29.0 ± 8.37kg/m2) was slightly lower than measured BMI (29.1 ± 8.38kg/m2) (p=0.4). Eighty percent of participants reported a BMI in the same category in which their BMI was measured. Pearson's correlation coefficient for height (0.96, p<0.001), weight (0.99, p<0.001), and BMI (0.99, p<0.001) were high. Reproductive age women accurately reported their height and weight.

The altered pharmacokinetics of cetrorelix in obese women may lead to premature ovulation during ART, and this could be one of the mechanisms that results in increased cycle cancelation in this group of women. In accordance with the higher gonadotropin requirements for obese women undergoing ART, weight-based dosing of GnRH antagonists may be required.