Oo. Adesanya et al., CELLULAR-LOCALIZATION AND SEX STEROID REGULATION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN MESSENGER RIBONUCLEIC-ACIDS IN THE PRIMATE MYOMETRIUM, The Journal of clinical endocrinology and metabolism, 81(7), 1996, pp. 2495-2501
Insulin-like growth factors (IGF)-I and -II are abundant in the primat
e myometrium and are implicated in the sex steroid-induced growth of t
his tissue. To evaluate the potential for modulation of IGF action in
the primate myometrium by locally produced IGF binding proteins (IGFBP
s), we examined the cellular localization and sex steroid regulation o
f IGFBPs 1-5 in the nonhuman primate uterus. Ovariectomized rhesus mon
keys were treated with placebo, estradiol (E(2)), or E(2) and progeste
rone (P-4) (E(2) and P-4) for 2 weeks, after which their uteri were re
moved and cut into thin serial sections for analysis by in situ hybrid
ization. IGFBP-1 messenger RNA (mRNA) was not detected in control or E
(2)-treated uteri but was found in a few unidentified cells in the E(2
) and P-4-treated group. IGFBP-2, -3, -4, and -5 mRNAs were all expres
sed by myometrial smooth muscle cells but each displayed distinctive p
atterns of regulation by sex steroids. IGFBP-2 was barely detectable i
n control myometrium, was significantly increased by E, and even more
significantly by E(2) and P-4. IGFBP-4 and 5 mRNAs were readily detect
able in control myometrium and significantly increased by E(2) treatme
nt. The addition of P-4 to E(2) treatment did not produce a significan
tly greater augmentation in IGFBP-4 or 5 mRNA level compared with E(2)
alone. IGFBP-3 mRNA was abundant in the control myometrium, but in co
ntrast to other IGFBPs was significantly reduced by approximately 75%
in smooth muscle cells by E(2) and by E(2) and P-4 treatment. Interest
ingly, however, IGFBP-3 mRNA was increased in the uterine vascular end
othelium by E(2) and by E(2) and P-4 treatment. In summary, this study
has shown that four of the six known IGFBPs are highly expressed in t
he primate myometrium, and that their expression is differentially reg
ulated by sex steroids. The cellular and sex steroid-regulated pattern
of IGFBP-2 gene expression is very similar to that of IGF-I, as previ
ously determined in these same myometrial samples. Both IGF I and IGFB
P-2 are dependent on E(2) for significant myometrial expression, and b
oth are further augmented by the addition of P-4 to E(2) treatment. Ut
erine smooth muscle IGFBP-3 mRNA levels are negatively regulated, wher
eas IGFBP-4 and -5 mRNA levels are positively regulated by E(2); none
of these myometrial IGFBPs appears sensitive to the effects of P-4. Th
e present observations, together with our previous data from the same
animals, demonstrate that the primate myometrial smooth muscle cell ex
presses mRNAs for IGF-I and -II, IGF-I and -II receptors, as well as e
xpresses mRNAs for IGFBP-2, -3, -4, and -5. These data provide evidenc
e for complex local interactions between IGF system components regulat
ed by estrogen and progesterone.