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.
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0678, USA.
Felix
F
Beuschlein
Chris
C
Mutch
David L
DL
Bavers
Yvonne M
YM
Ulrich-Lai
William C
WC
Engeland
Catherine
C
Keegan
Gary D
GD
Hammer
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