Expression of the IGF and the aromatase/estrogen receptor systems in human adrenal tissues from early infancy to late puberty: implications for the development of adrenarche.
Adrenarche is a process of postnatal sexual maturation occurring in higher primates, in which there is an increase in the secretion of adrenal androgens. It is the consequence of a process of postnatal organogenesis characterized by the development of a new zone in the adrenal cortex, the zona reticularis (ZR). The mechanism of this phenomenon remains poorly understood, suggesting that it might be a multifactorial event. A relationship between circulating IGF-I, insulin sensitivity, and adrenal androgens has been postulated. Boys and girls have different patterns of changes in insulin sensitivity at puberty, perhaps secondary to differences in the estrogen milieu. Estrogen effects may also play a role in premature adrenarche. Peripheral or local IGF-1 actions could regulate adrenal progenitor cell proliferation and migration. Since adrenal progenitor cells as well as IGF-I and the IGF-R1 are located in the outer zone of the adrenal cortex during childhood and adolescence, this peripheral cell layer, below the capsule, may contain undifferentiated progenitor cells. Therefore, the IGF-R1 signaling pathway might positively modulate the proliferation and migration of adrenal progenitor cell to stimulate the development of adrenal zones, including ZR. However, no evidence of a direct action of IGF-I on ZR was found. In addition, a role for estrogens in the ontogenesis of ZR is suggested by the presence of aromatase (CYP19) in the subcapsular zona glomerulosa and in the adrenal medulla. Estrogens produced locally could act on ZR by interacting with estrogen receptor beta (ERbeta), but not alpha, and membrane estrogen receptor GPR-30. An estradiol-induced increase in DHEA/cortisol ratio was indeed seen in cultures of adrenocortical cells from post-adrenarche adrenals. In summary, several lines of evidence point to the action of multiple factors, such as local adrenal maturational changes and peripheral metabolic signals, on postnatal human adrenal gland ZR formation.
Belgorosky
Alicia
A
Endocrinology Department, Garrahan Pediatric Hospital, Buenos Aires, Argentina. abelgo@elsitio.net
Baquedano
María Sonia
MS
Guercio
Gabriela
G
Rivarola
Marco A
MA
D000293:Adolescent; D000311:Adrenal Glands / Q000254:growth & development* / Q000378:metabolism*; D050499:Adrenarche / Q000502:physiology*; D001141:Aromatase / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007328:Insulin / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D011627:Puberty / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis; D013002:Somatomedins / Q000096:biosynthesis*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C109584:GPER1 protein, human; D007328:Insulin; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D013002:Somatomedins; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D001141:Aromatase; D017526:Receptor, IGF Type 1
J Mol Endocrinol. 2005 Oct;35(2):245-56
16216906
Steroids. 1997 Jan;62(1):62-72
9029717
Steroids. 2002 May;67(6):471-5
11960623
Pediatr Res. 2005 Sep;58(3):451-8
16148056
Am J Obstet Gynecol. 1983 Jun 15;146(4):417-29
6344640
J Clin Endocrinol Metab. 1988 Feb;66(2):422-9
2448331
Trends Endocrinol Metab. 2005 Oct;16(8):362-7
16125968
J Clin Endocrinol Metab. 2002 Apr;87(4):1819-28
11932324
J Clin Endocrinol Metab. 2007 Jun;92(6):2215-22
17405842
J Clin Endocrinol Metab. 1999 Dec;84(12):4739-41
10599744
J Clin Endocrinol Metab. 1992 Jul;75(1):308-14
1619023
Endocr Rev. 1997 Jun;18(3):378-403
9183569
J Clin Endocrinol Metab. 1995 Jan;80(1):172-8
7829608
J Clin Endocrinol Metab. 1999 Jun;84(6):2037-42
10372707
Mol Endocrinol. 1996 May;10(5):585-98
8732689
J Clin Endocrinol Metab. 2002 Jan;87(1):398-403
11788683
J Clin Endocrinol Metab. 1994 Mar;78(3):549-54
8126125
J Neurosci. 2000 Mar 1;20(5):1694-700
10684871
J Clin Endocrinol Metab. 1996 Nov;81(11):3892-7
8923834
J Clin Endocrinol Metab. 2002 Dec;87(12):5604-9
12466359
J Clin Endocrinol Metab. 2003 Mar;88(3):1389-93
12629134
Steroids. 1997 Feb;62(2):258-65
9055386
Endocrinol Metab Clin North Am. 1991 Mar;20(1):71-83
2029889
J Clin Endocrinol Metab. 1988 Aug;67(2):234-7
3392161
Horm Res. 1999;51(5):238-41
10559668
J Clin Endocrinol Metab. 2001 May;86(5):2258-62
11344236
J Clin Endocrinol Metab. 2002 Jan;87(1):136-43
11788637
J Clin Endocrinol Metab. 1996 Sep;81(9):3173-6
8784064
Acta Paediatr Suppl. 1999 Dec;88(433):60-6
10626547
Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10619-23
7479852
Biol Reprod. 1996 Feb;54(2):497-505
8788204
Front Biosci. 2001 Oct 01;6:D1379-91
11578956
Biochem Biophys Res Commun. 2006 Jan 13;339(2):548-53
16307725
J Clin Endocrinol Metab. 1998 Oct;83(10):3558-62
9768664
Postgrad Med J. 1979 May;55(643):353-7
382168
Science. 1987 Apr 10;236(4798):193-7
3563497
Science. 2000 Sep 22;289(5487):2122-5
11000114
J Clin Endocrinol Metab. 2002 Mar;87(3):1162-9
11889181
J Clin Endocrinol Metab. 1993 Nov;77(5):1184-9
8077311
J Cell Biochem. 1998 Sep 1;70(3):323-9
9706869
Endocrinology. 2000 Feb;141(2):649-56
10650946
Endocr J. 2000 Dec;47(6):723-30
11228047
Endocr Rev. 1998 Apr;19(2):101-43
9570034
J Clin Endocrinol Metab. 2002 Feb;87(2):791-7
11836323
J Biol Chem. 1978 Jul 25;253(14):4841-3
27508
Pediatr Res. 1999 Mar;45(3):384-8
10088659
J Clin Invest. 1994 Dec;94(6):2475-80
7989605
J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):211-7
12650718
Biochem Pharmacol. 1998 Jul 15;56(2):163-71
9698069
J Endocrinol. 1998 Sep;158(3):409-17
9846170
Lab Invest. 1970 Jun;22(6):513-27
5423978
Endocr Relat Cancer. 2003 Jun;10(2):331-45
12790794
Endocr Rev. 1997 Dec;18(6):774-800
9408743
Pediatr Res. 2000 Sep;48(3):384-8
10960508
J Endocrinol. 2004 Jan;180(1):125-33
14709151
Endocrinology. 2005 Feb;146(2):889-900
15550505
J Clin Endocrinol Metab. 1998 Oct;83(10):3695-701
9768686