Gestational and neonatal-onset hypothyroidism alters androgen receptor status in rat prostate glands at adulthood.
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) to 14 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.


CONCLUSIONS
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.
Aruldhas
Michael Maria
MM
Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, Tamil Nadu, India. aruldhasmm@gmail.com
Ramalingam
Neelamohan
N
Jaganathan
Anbalagan
A
John Sashi
Arokya Mary
AM
Stanley
Jone Arulrajadurai
JA
Nagappan
Arumugam Suriyam
AS
Vasavan
Jyothilakshmi
J
Kannan
Annapoorna
A
Seshadri
Venkatesh Nagamangalam
VN
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D004958:Estradiol / Q000097:blood; D005260:Female; D007037:Hypothyroidism / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D008713:Methimazole; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000097:blood; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D011944:Receptors, Androgen; D014284:Triiodothyronine; D013739:Testosterone; D004958:Estradiol; D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine