Intrapituitary adenoviral administration of 7B2 can extend life span and reverse endocrinological deficiencies in 7B2 null mice.
The prohormone convertase PC2 requires the aid of a helper protein, known as 7B2, for production of active enzyme. Deletion of 7B2 results in a lethal phenotype resembling Cushing's disease. In this study, we have investigated the effect of a single low dose of recombinant adenovirus vector encoding 7B2 and delivered directly to the pituitary of 7B2 nulls on pituitary ACTH, plasma ACTH, corticosterone, alpha MSH and glucose, and survival time. We show that after injection of recombinant adenovirus encoding 27-kDa 7B2 into 7B2 nulls, transgene expression, as measured by RIA for 7B2, exhibits a transient elevation in the pituitary and blood, with a slight but significant elevation of PC2 activity in pituitaries of 7B2 nulls and a drop in the level of circulating ACTH concomitant with a small increase in circulating alpha MSH. The level of circulating blood glucose was increased, and that of corticosterone was decreased. Lastly, slight but significantly prolonged survival times were observed. These data showing partial rescue of 7B2 nulls support the idea that adenoviral administration of 7B2 will represent an effective means to study the role of this interesting neuroendocrine protein on endocrine function in vivo.
Sarac
Miroslav S
MS
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Windeatt
Simon
S
Castro
Maria G
MG
Lindberg
Iris
I
D000256:Adenoviridae / Q000235:genetics*; D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004700:Endocrine System Diseases / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D051859:Neuroendocrine Secretory Protein 7B2; D010902:Pituitary Gland / Q000201:enzymology / Q000502:physiology*; D010907:Pituitary Hormones / Q000235:genetics* / Q000502:physiology; D045706:Proprotein Convertase 2; D013381:Subtilisins / Q000096:biosynthesis / Q000235:genetics; D000521:alpha-MSH / Q000097:blood; D001616:beta-Galactosidase / Q000235:genetics
D000914:Antibodies, Viral; D001786:Blood Glucose; D009419:Nerve Tissue Proteins; D051859:Neuroendocrine Secretory Protein 7B2; D010907:Pituitary Hormones; D000521:alpha-MSH; D000324:Adrenocorticotropic Hormone; D001616:beta-Galactosidase; D013381:Subtilisins; D045706:Proprotein Convertase 2; D003345:Corticosterone