Abstract
Cocaine-and Amphetamine Regulated Transcript (CART) peptide is expressed in the brain, endocrine and neuroendocrine systems and secreted into the serum. It is thought to play a role in regulation of hypothalamic pituitary functions. Here we report a spatial and temporal analysis of Cart expression in the pituitaries of adult and developing normal and mutant mice with hypopituitarism. We found that Prop1 is not necessary for initiation of Cart expression in the fetal pituitary at e14.5, but it is required indirectly for maintenance of Cart expression in the postnatal anterior pituitary gland. Pou1f1 deficiency has no effect on Cart expression before or after birth. There is no 1:1 correspondence between CART and any particular cell type. In neonates, CART is detected primarily in non-proliferating, POU1F1-positive cells. CART is also found in some cells that express TSH and GH suggesting a correspondence with committed progenitors of the POU1F1 lineage. In summary, we have characterized the normal temporal and cell specific expression of CART in mouse development and demonstrate that postnatal CART expression in the pituitary gland requires PROP1.
Highlights
Cocaine-and Amphetamine Regulated Transcript (CART) is expressed in several organs of the neuroendocrine and endocrine system including the pituitary gland, brain, adrenal gland, and the somatostatin producing cells of the pancreatic islets [1,2,3,4]
CART is expressed in the developing anterior and posterior pituitary gland If Cart were a direct target of Prop1, we would expect Cart expression to be activated in a spatial and temporal manner coincident or overlapping with Prop1 expression in normal mice and absent or reduced in Prop1df/df mutants
There are fewer cells that stain for CART in the anterior lobe of Prop1df/df at e16.5, but the anterior lobe is hypoplastic at that time
Summary
CART is expressed in several organs of the neuroendocrine and endocrine system including the pituitary gland, brain, adrenal gland, and the somatostatin producing cells of the pancreatic islets [1,2,3,4]. CART is most abundant in the hypothalamus [5]. Two different splice variants of the Cart transcript result in the production of two pro-peptides of different lengths, called proCART 1–89 and proCART 1–102. CART 55–102 is the predominant form in the anterior pituitary gland [5,6,7,8,9,10,11,12]. CART peptides may have a hormonal role as they are found in the pituitary portal blood system and peripheral blood [13], in addition to the anterior and posterior pituitary lobes [1, 14]
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