Abstract
There is increasing evidence that cocaine- and amphetamine-regulated transcript (CART) peptide is abundantly expressed in the anterior pituitary of birds and mammals, suggesting that CART peptide may be a novel pituitary hormone and its expression and secretion is likely controlled by the hypothalamic factor(s). To substantiate this hypothesis, using chicken as an animal model, we examined the effects of gonadotropin-releasing hormone (GnRH) on pituitary CART secretion and expression and investigated whether GnRH could modulate plasma CART levels. The results showed that: (1) chicken GnRH (GnRH1 and GnRH2) could potently stimulate CART peptide secretion in intact pituitaries incubated in vitro, as detected by Western blot; (2) GnRH could also stimulate CART mRNA expression in cultured pituitary cells, as revealed by quantitative real-time polymerase chain reaction (qPCR) assay; (3) GnRH actions on pituitary CART expression and secretion are likely mediated by GnRH receptor coupled to the intracellular Ca2+, MEK/ERK, and cAMP/PKA signaling pathways; and (4) plasma CART levels are high in chickens at various developmental stages (1.2–3.5 ng/ml) and show an increasing trend towards sexual maturity, as detected by enzyme-linked immunosorbent assay (ELISA). Moreover, plasma CART levels could be significantly induced by intraperitoneal administration of GnRH in chicks. Taken together, our data provide the first collective evidence that CART peptide is a novel pituitary hormone and its expression and secretion are tightly controlled by hypothalamic GnRH, thus likely being an active player in the hypothalamic-pituitary-gonadal (HPG) axis.
Highlights
It is well documented that cocaine- and amphetamine-regulated transcript (CART), an anorectic peptide of 41- or 48-amino acids with three intra-molecular disulfide bonds, plays an important role in the regulation of feeding and energy balance in mammals (Rogge et al, 2008)
We revealed that a large proportion of CART-ir cells is present in chicken anterior pituitaries, and gonadotropin-releasing hormone (GnRH) stimulates CART secretion and expression in vitro
We found that chicken CART peptide is predominantly and abundantly expressed in the anterior pituitary (Cai et al, 2015)
Summary
It is well documented that cocaine- and amphetamine-regulated transcript (CART), an anorectic peptide of 41- or 48-amino acids with three intra-molecular disulfide bonds, plays an important role in the regulation of feeding and energy balance in mammals (Rogge et al, 2008). CART is expressed in other brain regions, the peripheral nervous system (PNS) and peripheral tissues of mammals including the anterior pituitary, ovary, and pancreas (Koylu et al, 1997; Jensen et al, 1999; Thim et al, 1999; Murphy et al, 2000; Kobayashi et al, 2004; Wierup et al, 2006; Ma et al, 2016), and is suggested to be involved in the regulation of many other physiological processes, such as drug reward and reinforcement, stress, pancreatic secretion, bone remodeling, and ovarian follicle development and steroidogenesis (Kobayashi et al, 2004; Elefteriou et al, 2005; Sen et al, 2007; Rogge et al, 2008; Abels et al, 2016). Blood CART levels are related to the energy balance status, such as pregnancy/lactation in rats (Vicentic et al, 2004; Smith et al, 2006; Vicentic, 2006)
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