Circulating Cocaine- and Amphetamine-regulated transcript (CART) peptide in subjects with abnormalities of the hypothalamo-pituitary axis
FD McDermott, SA Stanley, KG Murphy, MA Ghatei & SR Bloom
Cocaine and amphetamine regulated transcript (CART) is a hypothalamic neuropeptide with a role in the hypothalamo-pituitary adrenal axis (HPA) in rodents. However, the role of pituitary CART is poorly understood. Previous work in rodents has shown pituitary CART is regulated by corticotrophin-releasing hormone (CRH) and glucocorticoids. CRH increased pituitary CART release fifteen-fold. Adrenalectomised rats had significantly higher pituitary CART mRNA expression, pituitary CART immunoreactivity (CART-ir) content and plasma CART-ir concentration. This was attenuated by corticosterone treatment. This suggested that pituitary CART may play a role in HPA axis in rodents. The aim of this study was to determine the relationship between plasma ACTH and CART-ir in humans.
Thirty subjects were recruited and 170 plasma samples collected. Subjects include those with a normal HPA axis, Cushing's disease or hypopituitarism. We examined the correlation between plasma ACTH and CART-ir and the effects of exogenous glucocorticoids and CRH on CART-ir. Median plasma ACTH and CART-ir, measured by radioimmunoassay, were 34.28 and 38.95 picomoles per litre respectively. Plasma CART-ir was significantly correlated with plasma ACTH (r equals 0.253, p less than 0.005). CART-ir was reduced in hypopituitary subjects compared to normal subjects and those with Cushing's disease (Control: CART-ir equals 45.47 plus/minus 8.67 picomoles per litre, Cushing's disease: CART-ir equals 40.03 plus/minus 12.56 picomoles per litre and hypopituitary: CART-ir equals 25.54 plus/minus 4.97 picomoles per litre, p equals n.s.). Exogenous glucocorticoids did not significantly suppress either plasma ACTH or CART-ir. CRH did not significantly increase plasma ACTH and CART-ir. Inferior petrosal sinus sampling did not demonstrate a central to peripheral plasma CART-ir gradient.
There is a positive correlation between plasma ACTH and CART-ir in humans suggesting possible co-regulation. However, neither exogenous steroids nor CRH significantly altered circulating CART-ir. Further work is needed to ascertain the relationship between CART-ir and ACTH in humans.