Steroidogenic factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy.
While the orphan nuclear receptor steroidogenic factor-1 (SF-1) has been shown to function as an induction factor to define adrenocortical cell lineage, it remains unclear whether SF-1 plays an additional role as a growth promoting agent in the adult adrenal cortex. The proliferative potential of the adrenal cortex in adult SF-1(+/-) mice was examined using the model of compensatory adrenal growth following unilateral adrenalectomy (uADX). While the right adrenal gland of wild-type (wt) mice grew significantly after uADX, the adrenal of SF-1(+/-) mice exhibited a blunted, statistically nonsignificant weight increase. Accordingly, a profound increase in the proliferation marker proliferating cell nuclear antigen could be detected only in wt mice after uADX but not in the SF-1(+/-) mice. The proposed key regulator in adrenal compensatory growth, the recently cloned adrenal secretory serine protease was up-regulated in the remaining adrenal of wt mice, whereas this increase was blunted in SF-1(+/-) mice. While no differences in preadipocyte factor-1, the presumed marker of primitive adrenocortical cells, were detectable in the adrenals of wt and SF-1(+/-) mice, an increase in the ACTH receptor as well as agouti-related protein was observed only in wt animals but not in the SF-1(+/-) mice following uADX. Taken together, these results reflect a primary inability of adrenal cortical cells of SF-1(+/-) mice to undergo compensatory adrenal growth in response to uADX.
Beuschlein
Felix
F
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0678, USA.
Mutch
Chris
C
Bavers
David L
DL
Ulrich-Lai
Yvonne M
YM
Engeland
William C
WC
Keegan
Catherine
C
Hammer
Gary D
GD
D000311:Adrenal Glands / Q000254:growth & development* / Q000294:innervation; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D054369:Agouti-Related Protein; D000818:Animals; D002135:Calcium-Binding Proteins; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000032:analysis / Q000502:physiology*; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008811:Mice, Inbred DBA; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014176:Protein Biosynthesis; D011506:Proteins; D012333:RNA, Messenger / Q000032:analysis; D018043:Receptors, Corticotropin / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins / Q000032:analysis; D012697:Serine Endopeptidases / Q000235:genetics; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000502:physiology
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; C512925:Dlk1 protein, mouse; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D012333:RNA, Messenger; D018043:Receptors, Corticotropin; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D000324:Adrenocorticotropic Hormone; D012697:Serine Endopeptidases; C431509:adrenal secretory protease; D003345:Corticosterone