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Human chorionic gonadotropin (hCG) is a pregnancy marker
secreted by the placenta and it signals through the same
receptors as LH. hCG subunits are known to be expressed in
tissues other than placenta. Similarly, LH/hCG receptors
are also expressed in multiple tissues; however, the
physiological significance of this expression is unknown.
Free hCG
is efficiently secreted in vitro in
transfected cells and is highly expressed in many human
cancers; however, it is not known what are the biological
effects of free hCG in vivo. To study in vivo
consequences of elevated levels of free hCG and hCG
dimer in both male and female reproductive physiology, we
generated multiple lines of transgenic mice overexpressing
either individual or both the subunits of hCG using a
mouse metallothionein promoter I (MT1). While mice
expressing the glycoprotein hormone 
-subunit are
normal and fertile, both male and female transgenic mice
overexpressing only the hormone-specific hCG
subunit are infertile. The hCG subunit-expressing
transgenic female mice progressively develop varying
degrees of cystic ovaries, whereas the male transgenic
mice are infertile but do not present any discernible
phenotypes. In contrast, both the male and female
transgenic mice co-expressing high levels of the hCG
subunits (i.e., the hCG dimer) demonstrate multiple
reproductive defects. The male transgenic mice have
Leydig cell hyperplasia, very high levels of serum
testosterone, reduced testis size, dramatically enlarged
seminal vesicles, are infertile and display overly
aggressive behavior when caged with females. The female
transgenic mice are also infertile, have elevated levels
of serum estradiol, and progressively develop hemorrhagic
and cystic ovaries with thecal layer enlargement and
stromal cell proliferation and degenerating kidneys.
These results suggest that the in vivo biological effects
of ectopically expressed free hCG subunit are
distinct from those of the hCG dimer and are
gender-specific. These transgenic mice are useful models
to study the biology of free hCGb subunit and to further
analyze the gain of function effects of hCG during early
Leydig cell development and to study the roles of hCG in
ovarian and kidney pathophysiology and function.
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