Interaction of testosterone with inhibin alpha and betaA subunits to regulate prostate gland growth.
Testosterone regulation of prostate gland growth has been shown to involve reciprocal interaction with inhibin and activin. This study was therefore conducted to correlate the effect of testosterone on prostate gland proliferation and differentiation with the level of expression of inhibin alpha and betaA subunits. Immature dogs were treated with testosterone for 0, 3, 7, and 14 days and prostate gland growth was assessed by morphological and immunohistological localization of differentiation and proliferation markers. The results showed that testosterone treatment resulted in an initial significant increase in PCNA proliferation index by days 3 and 7, followed by a significant decrease by day 14 post-treatment. Interestingly, the decrease of cell proliferation was associated with structural and biochemical changes characteristic of glandular and stromal differentiation of the prostate gland. These changes include progressive glandular ductal canalization and inter-ductal stroma differentiation which were apparent from a gradual shift from vimentin expression to vimentin and alpha-actin expression. Testosterone also had a differential effect on inhibin alpha and beta subunits. Although testosterone treatment resulted in significant and constant inhibition of alpha subunit mRNA expression, it resulted in a significant increase of betaA mRNA expression by day 3, followed by a decrease by days 7 and 14. These results indicated that testosterone acts first to drive proliferation of undifferentiated prostatic cells and then to maintain a low proliferation turnover of differentiated cells. Because it has been shown that activin is an antagonistic regulator of androgens, the attenuated stimulatory effect of testosterone on cell proliferation by day 14 might be mediated, at least in part, by interplay between testosterone and activin.
Shidaifat
Falah
F
Department of Basic Veterinary Medical Sciences, Faculty of Veterinary Medicine, Jordan University of Science and Technology, Irbid, Jordan. falah@just.edu.jo
Al-Zuhair
Ibrahim
I
Bani-Ismail
Zuhair
Z
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D004285:Dogs; D028322:Inhibin-beta Subunits / Q000378:metabolism*; D007265:Inhibins / Q000378:metabolism*; D008297:Male; D011467:Prostate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013739:Testosterone / Q000502:physiology*
D012333:RNA, Messenger; C103008:inhibin beta A subunit; C094377:inhibin-alpha subunit; D013739:Testosterone; D007265:Inhibins; D028322:Inhibin-beta Subunits
Endocr Res. 2004 Aug;30(3):327-34
15554348
J Endocrinol. 1999 Sep;162(3):341-50
10467225
J Endocrinol. 1996 Apr;149(1):93-9
8676059
Cytokine Growth Factor Rev. 2003 Feb;14(1):5-16
12485615
Prostate. 2004 Feb 15;58(3):299-307
14743470
Rev Reprod. 2000 May;5(2):99-104
10864854
J Urol. 1999 Apr;161(4):1378-84
10081911
Methods. 2001 Dec;25(4):402-8
11846609
Exp Biol Med (Maywood). 2002 Feb;227(2):75-87
11815670
J Biol Chem. 2000 Feb 4;275(5):3206-12
10652306
Dev Biol. 2001 Sep 1;237(1):145-58
11518512
Endocrinology. 1999 Nov;140(11):5303-9
10537161
Life Sci. 2007 Feb 6;80(9):829-34
17157324
Endocrinology. 1999 Jan;140(1):3-5
9886799
Mol Endocrinol. 2004 Mar;18(3):696-707
14684851
Br J Urol. 1996 Jan;77(1):107-12
8653279
Cell Growth Differ. 2002 Jan;13(1):1-11
11801526
J Clin Endocrinol Metab. 1998 Mar;83(3):969-75
9506758
J Endocrinol. 1998 Apr;157(1):1-4
9614351
Endocrinology. 1996 Dec;137(12):5476-83
8940374
Prostate. 1998 Jan 1;34(1):34-43
9428386
J Biol Chem. 1995 Mar 17;270(11):6308-13
7890768
Endocr Rev. 1994 Jun;15(3):310-25
8076584
J Endocrinol. 1997 Sep;154(3):535-45
9379131
Endocrinology. 1988 Apr;122(4):1701-2
3345731
Life Sci. 2005 Oct 14;77(22):2752-9
15978633