TESTICULAR EXPRESSION OF INHIBIN AND ACTIVIN SUBUNITS AND FOLLISTATININ THE RAT AND HUMAN FETUS AND NEONATE AND DURING POSTNATAL-DEVELOPMENT IN THE RAT
G. Majdic et al., TESTICULAR EXPRESSION OF INHIBIN AND ACTIVIN SUBUNITS AND FOLLISTATININ THE RAT AND HUMAN FETUS AND NEONATE AND DURING POSTNATAL-DEVELOPMENT IN THE RAT, Endocrinology, 138(5), 1997, pp. 2136-2147
Inhibins, activins, and follistatins are all believed to play roles in
the regulation of FSH secretion by the pituitary and in the paracrine
regulation of testis function. Previous studies have resulted in conf
licting data on the pattern of expression of the inhibin/activin subun
its, and little information on expression of follistatin during fetal/
neonatal life. We have made use of new, highly specific monoclonal ant
ibodies and fixed tissue sections from fetal, neonatal, and adult rats
, and limited amounts of fetal and neonatal human testis, to undertake
a detailed immunocytochemical study of the pattern of expression of t
hese regulatory proteins. In the rat, positive immunostaining for the
alpha-subunit of inhibin (alpha) was first detectable on day 14.5 post
coitum (p.c.), the first day on which the testis could be morphologic
ally distinguished ham the ovary. During fetal life, the alpha-immunos
taining was most prominent in the fetal Leydig cells. In Sertoli cells
, alpha-immunostaining was slightly stronger on days 14.5 and 15.5 p.c
. compared with 16.5-20.5. After birth, alpha-immunostaining remained
intense in fetal Leydig cells but declined following their replacement
with their adult-type counterparts; in contrast, alpha-subunit increa
sed in Sertoli cells immediately after birth. Immunostaining with anti
bodies specific to beta B-subunit showed a similar pattern to that of
the alpha-subunit, except that positive immunostaining was first detec
table on day 16.5 p.c., 2 days later than immunostaining for the alpha
-subunit. The pattern of beta B-immunostaining in postnatal samples pa
ralleled that of the alpha-subunit. Immunostaining using antibodies ag
ainst the beta A-subunit did not produce any significant reaction prod
uct in any sample. Follistatin was undetectable in the fetal rat testi
s but appeared in the Leydig cells immediately after birth and its exp
ression remained intense throughout postnatal development and in adult
testis. No evidence was obtained for expression of either the inhibin
/activin subunits or follistatin in the germ cells, peritubular myoid
cells, or other interstitial cells in any of the sections examined. In
the human fetal testis, both alpha- and beta B-subunits were immunode
tectable at 16, 18, and 24 weeks gestation in Sertoli and Leydig cells
, with stronger immunostaining in Sertoli cells at 24 weeks. Postnatal
ly at 4 months, immunoexpression of the beta B-subunit was no longer d
etectable, whereas the alpha-immunostaining became weaker but was stil
l present in both Sertoli and Leydig cells. No positive immunostaining
for beta A-subunit or follistatin was detectable at any time point st
udied. In conclusion, we have shown that, in the rat testis, the major
ity of inhibin alpha-subunit and inhibin/activin beta B-subunit is imm
unolocalized to the fetal-type Leydig cells during fetal/neonatal life
but, following birth, immunoexpression in the Sertoli cells of both s
ubunits increases markedly while follistatin is immunodetectable only
postnatally.