scholarly journals Effect of nitric oxide on the expression of insulin-like growth factors and the insulin-like growth factor binding proteins throughout the lifespan of the human corpus luteum

Reproduction ◽  
2001 ◽  
pp. 865-873 ◽  
Author(s):  
G Iniguez ◽  
A Villavicencio ◽  
F Gabler ◽  
A Palomino ◽  
M Vega

The presence of insulin-like growth factors (IGF), IGF binding proteins (IGFBP) and IGF receptor type 1 (IGF-IR) in the human corpus luteum was investigated by examining the expression and production of related proteins throughout the lifespan of the corpus luteum and the action of nitric oxide upon their production. The expression of proteins in corpora lutea from the early, mid-and late luteal phases was assessed by immunohisto-chemistry, evaluated by a semi-quantitative analysis and the functional study was performed in corpus luteum explants incubated with nitric oxide donors. IGF-I and -II and IGFBP-1 and -3 were measured in the culture media by specific immunoassays. The results showed that IGF-I and -II, IGFBP-1 to -6 and IGF-IR were detected in the human corpus luteum throughout the luteal phase. Moreover, the expression and production of IGF-I and IGFBP-1 increased progressively from corpora lutea from the early to late luteal phases (P < 0.05), whereas the expression and production of IGFBP-2, -4 and -5 were significantly higher in corpora lutea from the mid-luteal phase (P < 0.05). No differences were observed in the expression of IGF-II, IGFBP-3 and -6 and IGF-IR throughout the lifespan of the corpus luteum. However, functional studies showed that nitric oxide donors elicited a stimulatory action on production of IGF-I in corpora lutea from the early luteal phase (80%) and on production of IGFBP-1 in corpora lutea from the late luteal phase (50%) (P < 0.05), whereas production of IGF-II and IGFBP-3 was not affected by nitric oxide. In conclusion, the components of the IGF-IGFBP system are expressed in the human corpus luteum throughout its lifespan. Nitric oxide regulates IGF-I and IGFBP-1 production, indicating that the growth factors may serve, at least in part, as mediators of the action of nitric oxide in the human corpus luteum.

Reproduction ◽  
2000 ◽  
pp. 293-302 ◽  
Author(s):  
KJ Woad ◽  
G Baxter ◽  
CO Hogg ◽  
TA Bramley ◽  
R Webb ◽  
...  

Previous studies have implicated insulin-like growth factors I and II (IGF-I and -II), in the regulation of ovarian function. The present study investigated the localization of mRNA encoding IGF-I and -II and the type 1 IGF receptor using in situ hybridization to determine further the roles of the IGFs within the bovine corpus luteum at precise stages of the oestrous cycle. Luteal expression of mRNA encoding IGF-I and -II and the type 1 IGF receptor was detected throughout the oestrous cycle. The expression of IGF-I mRNAvaried significantly during the oestrous cycle. IGF-I mRNA concentrations were significantly higher on day 15 than on day 10, and IGF-I mRNA in the regressing corpus luteum at 48 h after administration of exogenous prostaglandin was significantly greater than in the early or mid-luteal phase (days 5 and 10). In contrast, there was no significant effect of day of the oestrous cycle on expression of mRNA for IGF-II and the type 1 IGF receptor in the corpus luteum. Expression of IGF-II mRNA was localized to a subset of steroidogenic luteal cells and was also associated with cells of the luteal vasculature. mRNA encoding the type 1 IGF receptor was widely expressed in a pattern indicative of expression in large and small luteal cells. These data demonstrate that the bovine corpus luteum is a site of IGF production and reception throughout the luteal phase. Furthermore, this study highlights the potential of IGF-II in addition to IGF-I in the autocrine and paracrine regulation of luteal function.


1996 ◽  
Vol 148 (1) ◽  
pp. 59-67 ◽  
Author(s):  
W C Duncan ◽  
A S McNeilly ◽  
P J Illingworth

Abstract Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a specific inhibitor of a group of proteolytic enzymes known as matrix metalloproteinases. These enzymes have been widely implicated in the process of tissue remodelling. Extensive remodelling occurs in the corpus luteum during luteolysis unless human chorionic gonadotrophin (hCG) is produced by the early conceptus. This study aimed to investigate the expression and localisation of TIMP-1 in human corpora lutea during the luteal phase of the cycle and after luteal rescue with exogenous hCG to mimic the changes of early pregnancy. Human corpora lutea from the early (n = 4), mid- (n=4) and late (n=4) luteal phases and after luteal rescue by hCG (n=4) were obtained at the time of hysterectomy. Expression of TIMP-1 was investigated in these tissues by Western blotting, immunohistochemistry, Northern blotting and in situ hybridisation. Luteal cells of thecal origin were distinguished from those of granulosa origin by immunostaining for 17α-hydroxylase. A 30 kDa protein consistent with TIMP-1 was detected in human corpora lutea. This protein was localised to the granulosa lutein cells in all tissues examined. TIMP-1 mRNA was found in large quantities in all glands examined and this again localised to the granulosa lutein cells. The expression and localisation of TIMP-1 did not change throughout the luteal phase and was not altered by luteal rescue. The function of this uniform expression of TIMP-1 in the corpus luteum is not clear but these data suggest that the inhibition of structural luteolysis during maternal recognition of pregnancy is not mediated by regulation of TIMP-1 expression. Journal of Endocrinology (1996) 148, 59–67


1997 ◽  
Vol 22 (2) ◽  
pp. 95-100
Author(s):  
James D. Evans ◽  
Margaret C. Eggo ◽  
Ian A. Donovan ◽  
Simon R. Bramhall ◽  
John P. Neoptolemos

2003 ◽  
Vol 4 (4) ◽  
pp. 213-224 ◽  
Author(s):  
Liam J. Murphy

The insulin like growth factors (IGF-I and -II) are structurally and functionally related to insulin. While insulin is a key regulator of glucose homeostasis over the short term, emerging evidence suggests that the IGFs are involved in the longer term glucose homeostasis, possibly by modulating insulin sensitivity. Unlike insulin, the IGFs are present in most biological fluids as complexes with high affinity binding proteins, the insulin-like growth factor binding proteins (IGFBPs). The IGFBPs regulate the bioavailability of the IGFs. Of the six IGFBPs identified there is evidence from studies in transgenic mice that both IGFBP-1 and IGFBP-3 may have a role in glucose regulation.


Reproduction ◽  
2002 ◽  
pp. 501-508 ◽  
Author(s):  
A Villavicencio ◽  
G Iniguez ◽  
MC Johnson ◽  
F Gabler ◽  
A Palomino ◽  
...  

The aim of the present study was to investigate the action of insulin-like growth factor I (IGF-I) and insulin-like growth factor-binding protein 3 (IGFBP-3) on steroidogenesis and apoptosis in human corpus luteum during the midluteal phase. Slices from corpora lutea were incubated for 4 h with IGF-I or IGFBP-3. Progesterone, oestradiol, androstenedione and testosterone concentrations were determined by radioimmunoassay; caspase 3 expression was assessed by immunohistochemistry; bcl-2, bax and P(450arom) expression were assessed by RT-PCR; and apoptosis was detected by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. The results showed that addition of IGF-I stimulated progesterone production (150%, P < 0.01), oestradiol production (65%, P < 0.05) and bcl-2 gene expression (approximately 200%, P < 0.05), but decreased apoptosis (P < 0.05). In contrast, IGFBP-3 reduced steroid production and increased bax gene expression and the percentage of apoptotic cells (P < 0.05). Neither IGF-I nor IGFBP-3 had an effect on P(450arom) expression or on the concentrations of its substrates. However, maximum expression of caspase 3 was detected in corpus luteum during the midluteal phase. In conclusion, these results indicate that IGF-I and IGFBP-3 act as regulatory peptides of the function of the human corpus luteum during the midluteal phase. This action may be direct or mediated by steroid production or by bcl-2-bax expression.


1977 ◽  
Vol 73 (1) ◽  
pp. 115-122 ◽  
Author(s):  
I. A. SWANSTON ◽  
K. P. McNATTY ◽  
D. T. BAIRD

SUMMARY The concentration of prostaglandin F2α (PGF2α), progesterone, pregnenolone, oestradiol-17β, oestrone, androstenedione and testosterone was measured in corpora lutea obtained from 40 women at various stages of the menstrual cycle. The concentration of PGF2α was significantly higher in corpora lutea immediately after ovulation (26·7 ± 3·9 (s.e.m.) ng/g, P < 0·005) and in corpora albicantia (16·3 ± 3·3 ng/g, P < 0·005) than at any other time during the luteal phase. There was no correlation between the concentration of PGF2α and that of any steroid. The progesterone concentration was highest in corpora lutea just after ovulation (24·9 ± 6·7 μg/g) and in early luteal groups (25·7 ± 6·8 μg/g) but declined significantly (P < 0·05) to its lowest level in corpora albicantia (1·82 ± 0·66 μg/g). The concentration of oestradiol-17β in the corpus luteum and luteal weight were significantly greater during the mid-luteal phase than at any other stage (concentration 282 ± 43 ng/g, P < 0·05; weight 1·86 ± 0·18 g, P < 0·005). The results indicate that regression of the human corpus luteum is not caused by a rise in the ovarian concentration of PGF2α in the late luteal phase of the cycle.


2020 ◽  
Author(s):  
Vanessa Y Tan ◽  
Caroline J Bull ◽  
Kalina M Biernacka ◽  
Alexander Teumer ◽  
Laura Corbin ◽  
...  

AbstractCirculating lipids have been associated with breast cancer (BCa). This association may, in part, be due to an effect of lipids on insulin-like growth factors (IGFs), which have been reliably associated with BCa. In two-sample Mendelian randomization (MR) analyses, we found that low density lipoprotein (LDL-C) was associated with IGFBP-3 (beta:0.08 SD; 95%CI:0.02,0.15; p = 0.01, per SD increase in LDL-C) and IGFBP-3 was associated with postmenopausal BCa (OR:1.09; 95%CI:1.00,1.19; p = 0.05, per SD increase in IGFBP-3). We also found that triglycerides were associated with IGF-I (beta:-0.13SD; 95%CI:-0.22,-0.03, per SD increase in triglycerides) and that IGF-I was associated with overall BCa (OR:1.10;95%CI:1.02,1.18, per SD increase in IGF-I). Taken together, these results suggest that IGFBP-3 may be a potential causal step between LDL-C and postmenopausal BCa and IGF-I a potential causal for triglycerides. Our two-step MR results build on evidence linking circulating lipids and IGFs with BCa, however, multivariable MR analyses are currently unable to support this relationship due to weak instruments.


1987 ◽  
Vol 115 (3) ◽  
pp. R21-R23 ◽  
Author(s):  
S.R. Davis ◽  
Z. Krozowski ◽  
R.I. McLachlan ◽  
H.G. Burger

ABSTRACT We report inhibin α- and βA -subunit gene expression in the human corpus luteum and placenta using human α-subunit and bovine βA -subunit nucleic acid probes. In addition, we have demonstrated the presence of immunoreactive and bioactive inhibin in human corpora lutea. Our findings suggest that this tissue is a significant source of inhibin during the luteal phase of the normal human menstrual cycle.


1985 ◽  
Vol 104 (1) ◽  
pp. 149-151 ◽  
Author(s):  
M. C. Richardson ◽  
G. M. Masson

ABSTRACT Suspensions of luteal cells were prepared from samples of human corpora lutea obtained during the luteal phase of menstrual cycles. Addition of oxytocin (1 μmol/l) to the various cell preparations had no effect on either basal production of progesterone or on steroidogenic responses to a range of concentrations of gonadotrophin. J. Endocr. (1985) 104, 149–151


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