title: Ectopic Agouti protein overexpression increases stimulated corticosterone production without effect on adenylate cyclase activity in mouse adrenal cells.
abstract: OBJECTIVE
  The antagonism of Agouti protein (AP) and Agouti-related protein on melanocortin receptors suggests an inhibitory role in the regulation of steroidogenesis. However, we have previously demonstrated that ectopic AP overexpression increased restraint-induced corticosterone release and adrenal reactivity to ACTH in mice. A high steroidogenic response to ACTH may be a consequence of a stimulatory AP action on the adenylate cyclase (AC) and/or intracellular steroidogenic enzymes. The aim of the present study was to estimate the effect of ectopic AP overexpression on the activity of AC and steroidogenic intracellular enzymes.
  
  
  METHODS
  ACTH and forskolin were used for AC stimulation, and dibutyryl cAMP and progesterone were used for stimulation of intracellular steroidogenic enzymes in isolated adrenal cells in male C57Bl/6J mice of two Agouti genotypes: A(y)/a (ectopic AP overexpression) and a/a (absence of AP in all tissues).
  
  
  RESULTS
  ACTH and forskolin increased cAMP accumulation to the same extent in both A(y)/a and a/a mouse adrenal cells (P<0.001; ANOVA), but resulted in higher corticosterone production in A(y)/a mice (P<0.001 for ACTH and P<0.01 for forskolin; ANOVA). Dibutyryl cAMP- and progesterone-induced corticosterone production was higher in A(y)/a mice than in a/a mice (P<0.001 for dibutyryl cAMP and P<0.01 for progesterone; ANOVA).
  
  
  CONCLUSIONS
  Ectopic AP overexpression increased stimulated corticosterone production and intracellular steroidogenic enzyme reactivity to cAMP without an effect on AC activity.
authors.affiliation: Institute of Cytology and Genetics of the Russian Academy of Sciences, Pr. Lavrentjeva 10, Novosibirsk 630090, Russia. antonyna2000@yandex.ru
authors.forename: Antonyna Y
authors.initials: AY
authors.lastname: Shevchenko
authors.forename: Nadezhda M
authors.initials: NM
authors.lastname: Bazhan
authors.forename: Elena N
authors.initials: EN
authors.lastname: Makarova
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Yakovleva
authors.forename: Nelli R
authors.initials: NR
authors.lastname: Karkaeva
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003345:Corticosterone / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism; D005799:Genes, Dominant; D005838:Genotype; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D009154:Mutation; D011374:Progesterone / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C515183:a protein, mouse; D005576:Colforsin; D011374:Progesterone; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D003345:Corticosterone