Vasopressin does not mediate hypersensitivity of the hypothalamic pituitary adrenal axis during chronic stress.

The hypothesis that vasopressin (VP) becomes the main mediator of pituitary corticotroph responsiveness during chronic hypothalamic pituitary adrenal (HPA) axis activation was tested by examining the effect of pharmacologic VP receptor blockade on the adrenocorticotropic hormone (ACTH) and corticosterone responses of 14-day repeatedly restrained rats. In spite of the increased vasopressinergic activity, repeatedly restrained rats showed lower ACTH and corticosterone responses to 10 min white noise compared with handled controls. These responses were unchanged by injection of the nonpeptide-selective V1b receptor antagonist SSR149415 i.

The parvocellular vasopressinergic system and responsiveness of the hypothalamic pituitary adrenal axis during chronic stress.

Vasopressin (VP) secreted from parvocellular neurons of the hypothalamic paraventricular nucleus (PVN) stimulates pituitary adrenocorticotropic hormone (ACTH) secretion, through interaction with receptors of the V1b subtype (V1bR) in the pituitary corticotroph, mainly by potentiating the stimulatory effects of corticotrophin-releasing hormone (CRH). Chronic stress paradigms associated with corticotroph hyperresponsiveness lead to preferential expression of hypothalamic VP over CRH and upregulation of pituitary V1bR, suggesting that VP has a primary role during adaptation of the hypothalamic pituitary adrenal (HPA) axis to long-term stimulation. However, studies using pharmacological or genetic ablation of V1bR have shown that VP is required for full ACTH responses to some stressors, but not for the sensitization of ACTH responses to a novel stress observed during chronic stress.

Dimerization between vasopressin V1b and corticotropin releasing hormone type 1 receptors.

1. Increasing evidence indicates that guanyl protein coupled receptors (GPCRs), including members of the vasopressin (VP) receptor family can act as homo- and heterodimers. Regulated expression and interaction of pituitary VP V1b receptor (V1bR) and corticotropin releasing hormone receptor type 1 (CRHR1) are critical for hypothalamic pituitary adrenal (HPA) axis adaptation, but it is unknown whether this involves physical interaction between these receptors.

Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity.

Both human linkage studies and MC3R knockout mouse models suggest that the MC3R may play an important role in energy homeostasis. Here we show that among 355 overweight and nonoverweight children, 8.2% were double homozygous for a pair of missense MC3R sequence variants (Thr6Lys and Val81Ile).

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression.

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling.

Ontogeny of corticotropin-releasing hormone binding in anterior pituitaries of fetal sheep.

Objectives: Previous studies have shown that anterior pituitary expression of corticotropin-releasing hormone type 1 receptor (CRH-R1) decreases during late gestation. This study sought to determine whether this reduction is from a decrease in the number of cells expressing CRH receptors or a decrease in the number of CRH receptors per cell.

Methods: Fetuses were studied at 100 days' gestational age (100 dGA), 120 dGA, or 140 dGA.

The role of hypothalamic input on corticotroph maturation in fetal sheep.

Corticotropin-releasing hormone receptor type 1 (CRH-R1) expression and vasopressin type 1b (V1b) receptor protein decrease in late-gestation fetal sheep. Because hypothalamo-pituitary disconnection (HPD) has been demonstrated to prevent the morphological maturation of corticotrophs, we hypothesized that hypothalamic input is necessary for the maturational changes in CRH-R1 and V1b receptor levels. We measured CRH-R1 and V1b receptor expression in the anterior pituitaries of fetuses at 140 days gestational age (dGA) that underwent HPD or sham surgery at 120 dGA.

Ontogeny and effect of cortisol on vasopressin-1b receptor expression in anterior pituitaries of fetal sheep.

Corticotroph responsiveness to arginine vasopressin (AVP) increases during late gestation in fetal sheep. The mechanism of this increase in AVP responsiveness is currently unknown but could be related to an increase in vasopressin type 1b (V1b) receptor expression in the pituitary during development. To determine if there are ontogenic changes in V1b receptor expression that may help explain the changes in ACTH responses to AVP, we studied pituitaries from three groups of fetal sheep [100, 120, or 140 days gestational age (dGA)].

Attenuation of corticotropin-releasing hormone and arginine vasopressin responsiveness during late-gestation pregnancy in sheep.

Responsiveness of the hypothalamo-pituitary-adrenal axis is decreased during pregnancy. Therefore, the objective of the present study was to determine if responsiveness at the level of individual corticotrophs to corticotropin-releasing hormone (CRH) or arginine vasopressin (AVP) is decreased during pregnancy in sheep. Anterior pituitaries (APs) were collected from pregnant and nonpregnant ewes.