Biology Reference
In-Depth Information
taneous rEPO treatment in mothers with postpartum anemia [126]. These data
suggest that maternal circulating EPO concentrations influence milk EPO con-
centrations or that EPO production - after the onset by a tissue-specific regu-
lator - can also be stimulated by hypoxia or anemia. The implication of milk-
borne EPO was discussed earlier. EPO may also have an autocrine or paracrine
function in the breast, since weak EPOR immunoreactivity is present in mam-
mary duct epithelial cells regardless of the lactating state [127]. Further stud-
ies may elucidate the para- or autocrine function and regulation of EPO in the
mammary gland.
Male reproductive organs
While clinical effects of rEPO on the hypothalamic-pituitary-testicular axis in
men are reported, no data on the expression of EPO and EPOR in the human
male reproductive organs are available [149]. Animal data suggest a role of
EPO in male reproductive organs.
In rats, EPO mRNA is expressed in testis and localized in Sertoli and per-
itubular myoid cells, but no EPO mRNA is detected in Leydig cells [150, 151].
In both Sertoli and peritubular myoid cells,
EPO
gene expression can be
induced by CoCl
2
.
EPO
gene expression responds to hormones
in vitro
in a
cell-specific manner: While follicle-stimulating hormone induces EPO mRNA
levels in Sertoli cells, testosterone suppresses
EPO
gene expression in per-
itubular myoid cells (LC-540 cells) [151]. Rat Leydig cells express EPOR, and
binding of rEPO stimulates testosterone production
in vitro
[152].
Another insight into the biology of EPO in the male reproductive system
comes from studies in mice. EPO is expressed in the murine testis and epi-
didymis. EPO mRNA levels in epididymis are approximately seven-fold high-
er than in testis, both independent of the presence of testosterone or estrogen.
EPO expression levels increase more significantly in the epididymis than in
the testis in response to hypoxia, indicating a tissues-specific regulatory mech-
anism for
EPO
gene expression. Under continuous hypoxic stimulation, EPO
mRNA expression in testis and epididymis peaks after four hours, but decreas-
es at eight hours. In the murine epididymis, EPO mRNA expression increases
three-fold during three and nine weeks of postnatal development, but remains
on a plateau between six and nine weeks when male mice are capable of fer-
tilization. After induction of EPO gene expression, EPO producing cells were
identified by
in situ
hybridization in the interstitial space of ductus epididymis,
but not in the duct epithelium. Data on the expression of EPOR are very lim-
ited. So far, EPOR mRNA expression is detected in murine epididymis, with-
out changes in the expression levels during sexual maturation [153]. The exact
identification of EPOR-expressing cells in the epididymis will be crucial to
understand the physiological function of EPO in epididymis. It has been spec-
ulated that EPO may not be directly involved in sperm maturation, but may
rather support the duct function through paracrine action [153].
