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Gestational and neonatal‐onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood
Author(s) -
Aruldhas Michael Maria,
Ramalingam Neelamohan,
Jaganathan Anbalagan,
John Sashi Arokya Mary,
Stanley Jone Arulrajadurai,
Nagappan Arumugam Suriyam,
Vasavan Jyothilakshmi,
Kannan Annapoorna,
Seshadri Venkatesh Nagamangalam
Publication year - 2009
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21101
Subject(s) - endocrinology , medicine , prostate , androgen receptor , fetus , thyroid , gestation , androgen , hormone , pregnancy , biology , prostate cancer , cancer , genetics
BACKGROUND Infertility associated with congenital and early childhood hypothyroidism is an important reproductive health problem in men. Nevertheless, the exact mechanism underlying hypothyroidism‐induced changes in the prostate gland, an androgen‐dependent organ that contributes a significant portion of the seminal plasma remains obscure. The present study tested the hypothesis “transient gestational‐ or neonatal‐onset hypothyroidism may have duration dependent and lobe specific effect on androgen receptor (AR) status in the prostate glands of adult rats.” METHODS Hypothyroidism was induced in pregnant and lactating rats by feeding 0.05% methimazole (MMI) through drinking water during fetal and neonatal milestones of testicular and prostatic development. Pregnant dams had MMI exposure from 9th day post‐coitum (dpc) to14 dpc (group II) or 21 dpc (group III). Lactating mothers had MMI exposure from day 1 post‐partum (dpp) to 14 dpp (group IV) or up to 29 dpp (group V). AR status in the dorsolateral and ventral prostate lobes (DLP and VP) of the pups was assessed by RT‐PCR, western blot and radio receptor assay. RESULTS AR mRNA expression consistently decreased in the DLP of all groups, whereas it increased in VP of group III and V rats. AR protein consistently decreased in both DLP and VP of all experimental rats. AR nuclear ligand‐binding activity diminished in groups II and IV, whereas it increased in groups III and V. CONCLUSION The results obtained support the proposed hypothesis and indicate that an optimum thyroid activity during pre‐ and neonatal period determines AR status in the prostate glands at adulthood. Prostate 70: 689–700, 2010. © 2009 Wiley‐Liss, Inc.