Interrelationships between follicle stimulating hormone and the growth hormone - Insulin-like growth factor - IGF-binding proteins axes in human granulosa cells in culture

被引:23
作者
Barreca, A [1 ]
Artini, PG [1 ]
Cesarone, A [1 ]
Arvigo, M [1 ]
DAmbrogio, G [1 ]
Genazzani, AR [1 ]
Giordano, G [1 ]
Minuto, F [1 ]
机构
[1] UNIV PISA,DIPARTIMENTO OSTET & GINECOL,PISA,ITALY
关键词
human granulosa cells; FSH; IGF; IGFBP; estradiol; ovarian follicles;
D O I
10.1007/BF03347856
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
As it has been hypothesized that IGF-binding proteins (IGFBPs) may have a role as autocrine/paracrine factors in regulating the local actions of the insulin-like growth factors (IGFs) in the ovary, we studied the production of the IGFBPs by human granulosa cells (GC) in culture and the role of IGFBP-3 in the modulation of ovarian cell responsiveness to IGF-I and FSH. To this purpose, human luteinizing GC were cultured in serum-free conditions for 24 h and subsequently submitted to increasing concentrations (2-8 nmol/l) of recombinant non-glycosylated or partially glycosylated IGF-BP-3 for 48 h, in the presence or absence of IGF-I, des(1-3)IGF-I - a truncated analog of human IGF-I with markedly reduced binding ability to IGFBPs - and FSH (5-20 mlU/ml). The results demonstrate that human GC release IGFBP-1-2 and -3 into the medium, and that FSH is able to inhibit this release, while GH is clearly inhibitory on IGFBP-1 and stimulatory on IGFBP3. Both IGF-I and des(1-3)IGF-I significantly (p<0.001) stimulate E(2) production by human GC in culture in a manner comparable to that of FSH in the dose range used. Preincubation for 2 h at 22 C with IGFBP-3, to allow the formation of the IGF-IGFBP complex, drastically reduced the stimulatory effect of IGF-I but not that of des(1-3)IGF-I. IGFBP-3 was also able to inhibit the stimulatory effect of FSH. These data show that: i) the IGF peptide is less active when bound to IGFBP-3; ii) as IGFBP-3 does not affect the potency cy of des(1-3)IGF-I, its inhibitory action is exerted upstream of the membrane receptor binding; iii) as the action of IGFBP-3 is exerted by binding the IGF peptide, its inhibitory effect on FSH points out the role of the locally produced IGF-II in potentiating the FSH action on human GC.
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页码:35 / 42
页数:8
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