Effect of polymorphisms in selected genes involved in pituitary-testicular function on reproductive hormones and phenotype in aging men.
BACKGROUND
Polymorphisms in genes involved in regulation, biosynthesis, metabolism, and actions of testicular sex hormones may influence hormone balance and phenotype of aging men.


OBJECTIVE
We investigated the relationships between polymorphisms in genes related to pituitary-testicular endocrine function and health status.


METHODS
Using cross-sectional baseline data, we conducted a multinational prospective cohort observational study consisting of a population survey of community-dwelling men.


METHODS
A total of 2748 men, aged 40-79 (mean +/- sd, 60.2 + 11.2) yr, were randomly recruited from eight European centers. Forty-three polymorphisms were genotyped in the following genes: androgen receptor (AR), estrogen receptor-alpha and -beta (ESR1 and ESR2), steroid 5alpha-reductase type II (SRD5A2), 17alpha-hydroxylase/17,20-lyase (CYP17A1), aromatase (CYP19A1), sex hormone-binding globulin (SHBG), LH beta-subunit (LHB), and LH receptor (LHCGR).


METHODS
We measured the associations between gene polymorphisms and endocrine, metabolic, and phenotypic parameters related to aging and sex hormone action.


RESULTS
Several polymorphisms in SHBG, ESR2, AR, CYP19A1, and LHB were significantly associated with circulating levels of SHBG, LH, total, free, and bioavailable testosterone and estradiol, the LH x testosterone product, and indices of insulin sensitivity. Apart from several previously reported associations between genes affecting estrogen levels and heel ultrasound parameters, no associations existed between polymorphisms and nonhormonal variables (anthropometry, blood lipids, blood pressure, hemoglobin, prostate symptoms, prostate-specific antigen, sexual dysfunction, cognition).


CONCLUSIONS
In aging men, polymorphisms in genes related to the pituitary-testicular endocrine function significantly influence circulating LH, testosterone, and estradiol levels, but the downstream effects may be too small to influence secondary phenotypic parameters.
Huhtaniemi
Ilpo T
IT
Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, Du Cane Road, London W12 0NN, United Kingdom. ilpo.huhtaniemi@imperial.ac.uk
Pye
Stephen R
SR
Holliday
Kate L
KL
Thomson
Wendy
W
O'Neill
Terence W
TW
Platt
Hazel
H
Payne
Debbie
D
John
Sally L
SL
Jiang
Min
M
Bartfai
György
G
Boonen
Steven
S
Casanueva
Felipe F
FF
Finn
Joseph D
JD
Forti
Gianni
G
Giwercman
Aleksander
A
Han
Thang S
TS
Kula
Krzysztof
K
Lean
Michael E J
ME
Pendleton
Neil
N
Punab
Margus
M
Silman
Alan J
AJ
Vanderschueren
Dirk
D
Labrie
Fernand
F
Wu
Frederick C W
FC
D000328:Adult; D000368:Aged / Q000502:physiology*; D000375:Aging / Q000502:physiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D030541:Databases, Genetic; D005060:Europe; D005787:Gene Frequency; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006304:Health Status; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010902:Pituitary Gland / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013737:Testis / Q000502:physiology*
D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D004247:DNA