F. Khamsi et Dt. Armstrong, INTERACTIONS BETWEEN FOLLICLE-STIMULATING-HORMONE AND GROWTH-FACTORS IN REGULATION OF DEOXYRIBONUCLEIC-ACID SYNTHESIS IN BOVINE GRANULOSA-CELLS, Biology of reproduction, 57(3), 1997, pp. 684-688
Follicle growth is regulated by the combined actions and interactions
of pituitary gonadotropic hormones and local intraovarian paracrine an
d/or autocrine agents, including the peptide growth factors, insulin-l
ike growth factor-I (ICF-I), and epidermal growth factor (EGF). The pr
esent study was undertaken to determine a) whether the previously demo
nstrated inhibitory effect of FSH on DNA synthesis was related to its
ability to cause cumulus mucification as a differentiated response inc
ompatible with continued proliferation, and b) whether increased IGF-b
inding proteins (IGFBP) secreted in response to FSH competed with IGF
receptors, thereby inhibiting response to exogenous IGF-I. To determin
e the effects of cumulus mucification in modulating the mitogenic resp
onse to IGF-I, two other agents that induce cumulus mucification by di
fferent mechanisms, EGF and dibutyryl cAMP (dbcAMP), were compared wit
h FSH. To determine the possible role of IGFBP in modulating the mitog
enic response to IGF-I, an IGF-I analogue that does not bind to IGFBP,
long arg(3)-IGF-I (LR3-IGF-I), was compared with native IGF-I for eff
icacy in stimulating DNA synthesis in the absence and presence of each
of the above agonists. Both ICF-I and LR3-IGF-I stimulated [H-3]thymi
dine incorporation in cumulus cells to a much greater extent than in m
ural granulosa cells, Incorporation in mural cells was increased by ea
ch of FSH, EGF, and dbcAMP acting by itself, and in most instances was
considerably enhanced by the combined action of these agents with eac
h of the ICF-I forms. In contrast, the considerably greater stimulator
y effect of both IGF-I and LR3-IGF-I on cumulus cells was markedly dec
reased by each of FSH, EGF, and dbcAMP. These findings suggest that th
e inhibition of IGF-I-stimulated DNA synthesis in cumulus cells is a c
onsequence of induction of cumulus cell differentiation (mucification)
by FSH and EGF rather than through competition between IGF-I receptor
and IGFBP secretion induced by these agents.