Rat Prokineticin Receptor 1 ELISA Kit

Primary pigmented nodular adrenal disease (PNNAD) is a rare cause of Cushing syndrome particularly during childhood and adolescence. Females are preferentially affected. The present work is aimed at assessing if there is a relationship between puberty and the development of Cushing syndrome due to PPNAD. We have followed an extended family with Carney complex (CNC) due to a dominantly inherited mutation of the gene encoding the regulatory subunit 1 alpha (R1A) of the protein kinase A (PRKAR1A). The large majority of family members presenting with Cushing syndrome due to PPNAD were women (six out of seven). One of them died of an adrenocortical carcinoma at age 27 years. Genetic screening of entire family allowed follow-up of those family members harboring the mutation but without clinical manifestations of hypercortisolism. During the last 2 years, three related adolescent girls developed subclinical hypercortisolism starting shortly after menarche. None of their male relatives carrying the same mutation showed abnormal adrenal function. The first abnormality noticed in the patients was loss of the normal circadian variation of cortisol production. A low dose dexamethasone test (Liddle's test) elicited a paradoxical increase in urinary excretion of free cortisol greater than 50% of basal values. Several months later, they complained of insidious manifestations of hypercortisolism including weight gain, hypertension and oligomenorrhea. They underwent laparoscopic bilateral adrenalectomy. Pathologically, the excised glands showed PPNAD. We conclude that female gender is a predisposing factor for expressing PPNAD. A paradoxical rise of urinary free cortisol (UFC) in response to dexamethasone is an early and specific laboratory marker of the disorder, allowing timely bilateral adrenalectomy which may not only prevent severe complications of hypercortisolism, but may also preclude the development of adrenocortical carcinoma.

PRKAR1A (R1A)-retinoic acid receptor-alpha (R1A-RAR alpha) is the sixth RAR alpha-containing fusion protein in acute promyelocytic leukemia (APL). Using the murine bone-marrow retroviral transduction/transformation assay, we showed that R1A-RAR alpha fusion protein could transform bone-marrow progenitor/stem cells. In gel-shift assays, R1A-RAR alpha was able to bind to a panel of retinoic acid response elements both as a homodimer and as a heterodimer with RXR alpha, and demonstrated distinct DNA-binding characteristics compared with wild-type RAR alpha/RXR alpha or other X-RAR alpha chimeric proteins. The ratio of R1A-RAR alpha to RXR alpha proteins affected the retinoic acid response element interaction pattern of R1A-RAR alpha/RXR alpha complexes. Studies comparing R1A-RAR alpha with R1A-RAR alpha(Delta RIIa) demonstrated that the RIIa protein interaction domain located within R1A was responsible for R1A-RAR alpha homodimeric DNA binding and interaction with wild-type R1A protein. However, the RIIa domain was not required for R1A-RAR alpha-mediated transformation because its deletion in R1A-RAR alpha(Delta RIIa) did not compromise its transformation capability. In contrast, introduction of point mutations within the RAR alpha portion of either R1A-RAR alpha or R1A-RAR alpha(Delta RIIa), previously demonstrated to eliminate RXR alpha interaction or treatment of transduced cells with RXR alpha shRNA or a RXR alpha agonist, reduced transformation capability. Thus, leukemic transformation by APL fusion protein PRKAR1A-RAR alpha is critically dependent on RXR alpha, which suggests RXR alpha is a promising target for APL. (Blood. 2010; 115: 643-652)