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P J Fielder

Publications and source records attributed to P J Fielder.

52 records · Page 3Linked to original sources
PubMed1992

Expression of serum insulin-like growth factors, insulin-like growth factor-binding proteins, and the growth hormone-binding protein in heterozygote relatives of Ecuadorian growth hormone receptor deficient patients.

Recently, an isolated population of apparent GH-receptor deficient (GHRD) patients has been identified in the Loja province of southern Ecuador. These individuals presented many of the physical and biochemical phenotypes characteristic of Laron-Syndrome and are believed to have a defect in the GH-receptor gene. In this study, we have compared the biochemical phenotypes between the affected individuals and their parents, considered to be obligate heterozygotes for the disorder. Serum GH, insulin-like growth factor I and II (IGF-I and IGF-II) levels were measured by RIA Insulin-like growth factor binding proteins. (IGFBPs) were measured by Western ligand blotting (WLB) of serum samples, following separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and relative quantitation of serum IGFBPs was performed with a scanning laser densitometer. Serum GH-binding protein (GHBP) levels were measured with a ligand-mediated immunofunctional assay using a monoclonal antibody raised against the GHBP. These values were then compared to values obtained from normal, sex-matched adult Ecuadorian controls, to determine if the above parameters were abnormal in the heterozygotes. The serum IGF-I levels of the GHRD patients were less than 13% of control values for adults and 2% for children. However, the IGF-I levels of both the mothers and fathers were not significantly different from that of the control population. The serum IGF-II levels of the GHRD patients were approximately 20% of control values for adults and 12% for the children. The IGF-II levels of the mothers were reduced, but were not significantly different from that of the control population. However, IGF-II levels of the fathers were significantly lower than those of controls (64% of control male levels). WLB analysis of serum IGFBP levels of the affected subjects demonstrated increased IGFBP-2 and decreased IGFBP-3, suggesting an inverse relationship between these IGFBPs. The GHRD patients who had the lowest serum IGFBP-3 levels (as measured by WLB) demonstrated a serum protease activity that could proteolyze 125I-IGFBP-3. GHRD patients who had higher serum IGFBP-3 levels lacked this serum protease activity. There were no differences in the serum IGFBP profiles of the mothers or the fathers for either IGFBP-2 or IGFBP-3, and serum from both groups lacked the ability to significantly proteolyze 125I-IGFBP-3. While GHRD patients had very low levels of serum GHBP, some patients did have measurable GHBP levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Characterization of the steroid-dependence of insulin-like growth factor-binding protein-2 synthesis and mRNA expression in cultured human endometrial stromal cells.

The insulin-like growth factors (IGF-I and -II) are believed to be important in endometrial differentiation and blastocyst nidation, and proteins that regulate IGF action (IGF-binding proteins, IGFBPs) are hormonally regulated in endometrium during the menstrual cycle. To characterize further steroid-dependence of the IGFBPs, we established endometrial stromal cells in culture in the absence and presence of oestradiol (E2) and progesterone (P) and examined the conditioned medium for IGFBPs by Western ligand blot analysis. Stromal cells constitutively synthesized IGFBP-3, IGFBP-2, a 27 kd, and a 24 kd IGFBP. In the presence of E2 and P, a 10- to 15-fold increase in IGFBP-2 was detected in the conditioned medium beginning after about 7 days in culture, when cells decidualized and steroid-mediated prolactin secretion began. Withdrawal of steroids resulted in a marked decrease in IGFBP-2, comparable to control levels, and cells increased their IGFBP-2 production when rechallenged with E2 and P. Total RNA was isolated from stromal cells, and Northern blot analysis using a cDNA probe specific for IGFBP-2 revealed differential expression of a 1.4 kb mRNA transcript in steroid-treated compared to control cells. The effects of progestational agents alone on IGFBP synthesis was also examined. Progesterone, medroxyprogesterone acetate and norethindrone all stimulated IGFBP-2 synthesis 12- to 15-fold compared to controls, and a progesterone receptor antagonist, RU 486, blocked the stimulatory effect of progesterone. IGFBP-2 synthesis was increased two-fold above controls by 17-alpha-hydroxyprogesterone, and RU 486 alone and hydrocortisone were without effect. Identification of IGFBP-2 in conditioned medium was made using IGFBP-specific antiserum. These data show that (a) endometrial stromal cells synthesize and secrete IGFBP-2, (b) IGFBP-2 protein synthesis is controlled by steroid hormones, (c) P, by interacting with its receptor, modulates IGFBP-2 synthesis and (d) expression of IGFBP-2 mRNA is controlled by sex steroids.

Autoradiography↗
PubMed1991

Regulation of serum insulin-like growth factors and their binding proteins in Ecuadorean patients with growth hormone receptor dysfunction (growth hormone insensitivity).

Regulation of serum insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and growth hormone (GH) binding protein (GHBP) has been investigated in Ecuadorean patients with GH receptor dysfunction (GHRD) and in their heterozygous relatives (parents). Serum IGF-I and IGF-II levels were measured by radioimmunoassay (RIA). IGFBPs were identified by Western ligand blotting of serum samples, following separation by sodium dodecyl sulphate polyacrylamide gel electrophoresis, and relative quantification was performed with a scanning laser densitometer. Serum GHBP levels were measured with a ligand-mediated immunofunctional assay (LIFA) using a monoclonal antibody raised against the GHBP. These values were then compared with values obtained from normal, sex-matched Ecuadorean controls. Serum IGF-I, IGF-II, IGFBP-3 and GHBP concentrations were markedly reduced and serum IGFBP-2 values increased in the patients with GHRD. Serum IGF-I and IGF-II values were positively correlated in the patients with GHRD, but were not related to the age of the patient. IGFBP-2 and IGFBP-3 concentrations were inversely correlated in the patients with GHRD. When analysed by age, however, IGFBP-2 was related inversely and IGFBP-3 related positively to the age of the patient. The serum IGF-II levels of the male heterozygotes were significantly reduced when compared with sex-matched controls, but considerable overlap with normal values was found. No other biochemical indices were significantly altered in either male or female heterozygotes. Thus, although GHRD is characterized by dramatic reductions in serum levels of GHBP, IGF-I, IGF-II and IGFBP-3, none of these assays provides a reliable biochemical marker for heterozygosity.

Biomarkers↗
PubMed1991

Growth hormone receptor deficiency (Laron syndrome): clinical and genetic characteristics.

Approximately 60 cases of GHRD (Laron syndrome) were reported before 1990 and half of these were from Israel. We have described 47 additional patients from an inbred population of South Ecuador and have emphasized certain clinical features including: markedly advanced osseous maturation for height age; normal body proportions in childhood but child-like proportions in adults; much greater deviation of stature than head size, giving an appearance of large cranium and small facies; underweight in childhood despite the appearance of obesity and true obesity in adulthood; blue scleras; and limited elbow extension. The Ecuadorean patients differed markedly and most importantly from the other large concentration, in Israel, by being of normal or superior intelligence, suggesting a unique linkage in the Ecuadorean population. The Ecuadorean population also differed in that those patients coming from Loja province had a markedly skewed sex ratio (19 females: 2 males), while those from El Oro province had a normal sex distribution (14 females: 12 males). The phenotypic similarity between the El Oro and Loja patients indicates that this abnormal sex distribution is not a direct result of the GHRD.

Body Constitution↗
PubMed1991

Differential effects of insulin-like growth factor (IGF)-I and IGF-II on the expression of IGF binding proteins (IGFBPs) in a rat neuroblastoma cell line: isolation and characterization of two forms of IGFBP-4.

The isolation and hormonal regulation of two low molecular weight insulin-like growth factor binding proteins (IGFBPs) present in the conditioned medium (CM) of the rat neuroblastoma cell line B104 cells has been performed. IGFBPs were purified by ZnSO4 precipitation, insulin-like growth factor-I 1IGF-I) affinity chromatography, and reverse phase HPLC. Final isolation and N-terminal analysis was accomplished by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroblotting to polyvinylidene difluoride membranes, and sequencing of the bound proteins. Two IGFBPs, with apparent Mr of 28K and 24K were coisolated and sequenced. Both proteins had identical N-terminal sequences and appear to be two forms of IGFBP-4. Treatment of the IGFBPs with endoglycosidase-F caused a shift in the apparent Mr of the 28K IGFBP to 24K. However, there was no change in the apparent Mr of the 24K IGFBP. The data from this study suggest that the IGFBP-4 exists as both a glycosylated and nonglycosylated protein. Treatment of B104 cells with IGF-I increased the expression of both the 24K and 28K IGFBPs and also resulted in the appearance of IGFBP-3 and an unknown IGFBP at 29K. When added to subconfluent cells, IGF-I was also mitogenic in B104 cells. Similar to IGF-I, IGF-II treatment increased cell number and resulted in the appearance of IGFBP-3 and the 29K IGFBP. However, IGF-II treatment resulted in a significant decrease (approximately 50%) in the 24K IGFBP and also decreased the 28K IGFBP. This decrease in the expression of the 24K and 28K IGFBPs was dose-dependent and was blocked by addition of IGF-I to the cells. When an IGF-II receptor antibody was added to the cells it mimicked the effects of IGF-II on B104 cells, suggesting that the inhibitory effects of IGF-II are mediated through the type II IGF receptor. Although both IGF-I and IGF-II affected the amount of the 24K IGFBP in the CM, neither peptide affected the expression of the messenger RNA for the 24K IGFBP. In conclusion, we have isolated two IGFBPs from the CM of B104 cells. Both the 24K and 28K IGFBPs appear to be isoforms of the same protein, and sequence data suggest these proteins are two forms of IGFBP-4. IGF-I increases the expression of both of these IGFBPs, whereas IGF-II decreases their expression.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1990

The little women of Loja--growth hormone-receptor deficiency in an inbred population of southern Ecuador.

BACKGROUND AND METHODS: Laron-type dwarfism, which is characterized by the clinical appearance of isolated growth hormone deficiency with elevated serum levels of growth hormone and decreased serum levels of insulin-like growth factor I (IGF-I), has been described in approximately 50 patients. This condition is caused by a deficiency of the cellular receptor for growth hormone, and it is transmitted as an autosomal recessive trait, as indicated by an equal sex distribution and a high rate of consanguinity in affected families. We studied 20 patients (19 females and 1 male, 2 to 49 years of age), from an inbred Spanish population in southern Ecuador, who had the clinical features of Laron-type dwarfism. RESULTS: Seventeen patients were members of two large pedigrees. Among the 13 affected sibships, there were 19 affected and 24 unaffected female siblings and 1 affected and 21 unaffected male siblings. The patients' heights ranged from 10.0 to 6.7 SD below the normal mean height for age in the United States. In addition to the previously described features, 15 patients had limited elbow extensibility, all had blue scleras, affected adults had relatively short extremities, and all four affected women over 30 years of age had hip degeneration. Basal serum concentrations of growth hormone were elevated in all affected children (30 to 160 micrograms per liter) and normal to moderately elevated in the adults. The serum level of growth hormone-binding protein ranged from 1 to 30 percent of normal; IGF-I concentrations were low--less than or equal to 7 micrograms per liter in the children and less than or equal to 66 micrograms per liter in the adults (normal for Ecuadorean women, 98 to 238). Serum levels of IGF-II and growth hormone-dependent IGF-binding protein-3 were also low. CONCLUSIONS: We describe an inbred population with a high incidence of growth hormone-receptor deficiency resulting in a clinical picture resembling Laron-type dwarfism but differing principally in showing a marked predominance of affected females. This population, of Mediterranean origin, may be genetically related to other reported populations with Laron-type dwarfism, but with the genetic defect linked to a trait resulting in the early fetal death of most affected males.

Adolescent↗
PubMed1990

Hypophysectomy eliminates and growth hormone (GH) maintains the midpregnancy elevation in GH receptor and serum binding protein in the mouse.

[125I]Iodomouse GH [( 125I]iodo-mGH) binding to samples of serum and hepatic microsomal membranes was measured in hypophysectomized pregnant, sham-operated pregnant, intact pregnant, and intact adult virgin mice. Surgeries were carried out on day 11 of pregnancy, and the animals were killed on day 14. The binding of mGH to both serum and hepatic microsomal membranes of intact virgin mice was much lower than to those of intact pregnant mice. In hypophysectomized mice, the mGH-binding capacity of both serum and hepatic microsomes decreased to values similar to those of nonpregnant mice. No significant differences were observed between intact and sham-operated pregnant animals in the maternal serum mGH concentration, the serum GH-binding protein concentration, or the hepatic GH receptor concentration. GH receptor and binding protein-encoding mRNAs were also higher in intact and sham-operated pregnant mice than in virgin and hypophysectomized mice. Hypophysectomized mice were treated with 200 micrograms/day bovine GH, administered by osmotic minipump; after 3 days of treatment, a significant elevation of hepatic GH receptor and serum GH-binding protein levels was observed. These results demonstrate an up-regulation of hepatic GH receptors and serum GH-binding protein by GH during pregnancy in the mouse.

Animals↗
PubMed1990

Characterization of insulin-like growth factor binding proteins (IGFBPs) during gestation in mice: effects of hypophysectomy and an IGFBP-specific serum protease activity.

Characterization of insulin-like growth factor binding proteins (IGFBPs) and their pituitary regulation were investigated in intact and hypophysectomized (HX) pregnant and nonpregnant mice. Serum samples were obtained from pregnant mice killed on days 5, 8, 10, 12, 14, and 18 of gestation and fetal mice killed on day 18 of gestation. Some animals were HX or sham operated (SH) on days 9, 11, and 14 of gestation; HX and SH control animals were killed 3 days post surgery. Identification and relative quantities of IGFBPs were determined by Western ligand blotting (WLB) of whole serum, or immunoprecipitated and/or deglycosylated serum, using [125I]IGF-II as the ligand. Serum IGF-I and -II concentrations were determined in both HX and SH day 14 pregnant, nonpregnant, and day 18 fetal mouse sera. WLB analysis of nonpregnant mouse serum demonstrated IGFBPs with apparent Mr of approximately 45-40, 31-27, and 24 K. The 45-40 K IGFBPs appeared to be the mouse equivalent of IGFBP-3, and one of the 31-27 K IGFBPs appeared to be IGFBP-2. The other IGFBPs present are not yet fully identified. During pregnancy, the amount of IGFBP-3 present in serum (as measured by WLB) gradually decreased to 42%, 17%, and 10% of virgin levels on days 5, 8, and 10 of gestation. The amount of IGFBP-3 present in pregnant serum after day 10 of gestation was not measurable by scanning laser densitometry. Additionally, an IGFBP of approximately 27 K appeared during gestation; after treatment with Endoglycosidase F, this IGFBP decreased to 24 K. The major IGFBP in fetal serum appeared to be IGFBP-2, with lesser amounts of IGFBP-3 and the 27 and 24 K IGFBPs. Hypophysectomy significantly decreased IGFBP-3, IGF-I, and IGF-II in nonpregnant mouse serum, increased the amount of IGFBP2 found in pregnant mouse serum, and had no effect on IGF-I or -II concentration in day 14 pregnant mouse serum. Incubation of nonpregnant serum with late (day 17) pregnant serum for 5 h at 37 C, decreased the amount of IGFBP-3 (as measured by WLB) in the mixed sample to 93% of the amount present in the nonmixed sample. Iodinated recombinant IGFBP-3 ([125I]human (h)IGFBP-3) was incubated with different mouse serum samples, and proteolytic fragments were visualized after separation by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Ethanol consumption during pregnancy in mice: effects on hormone concentrations.

Hormonal and metabolic responses to ethanol consumption were studied in pregnant Swiss Webster mice and their fetuses. On day 10 of pregnancy, mice were assigned to one of three liquid diet groups: 36% ethanol-derived calories fed ad libitum (ETOH); control liquid diet fed ad libitum (control); control liquid diet administered in the same amount as that consumed by the ETOH group on the same day of pregnancy [pair-fed controls (PF)]. Dams were killed on days 14-18 of pregnancy, and fetuses were collected on days 16-18. Serum mouse placental lactogen-II (mPL-II), prolactin (mPRL), growth hormone (mGH), insulin, and glucose concentrations were determined for each group. Ethanol consumption resulted in a significant reduction in fetal weight on day 18 of pregnancy. The maternal serum mPRL concentration was reduced in ETOH mice on days 16 and 17 of pregnancy when compared with control mice, but when compared with PF mice, it was significantly reduced only on day 16. Maternal and fetal serum insulin concentrations were reduced in ETOH mice when compared with control mice, but it is unclear whether this was a specific effect of ethanol consumption or due to reduced food intake. Maternal serum glucose concentrations were reduced in the ETOH mice but not as severely as in the PF mice. Ethanol consumption had no effect on maternal or fetal serum mPL-II and mGH concentrations. These data confirm that ethanol consumption during pregnancy results in fetal growth retardation, but they do not indicate any major effects of ethanol on mPL-II, mPRL, mGH, and insulin concentrations in either the mother or fetus.

Alcohol Drinking↗
PubMed1987

Effects of fasting on serum lactogenic hormone concentrations during mid- and late pregnancy in mice.

Hormonal and metabolic responses to fasting were studied in pregnant Swiss Webster mice. Food was removed from pregnant mice 12, 24, 36, or 48 h before death on day 12 or 15 of pregnancy. Serum mouse placental lactogen-II (mPL-II), mouse growth hormone (mGH), mouse prolactin (mPRL), free fatty acids (FFA), and glucose concentrations were determined for each group. In comparing fasted animals with fed controls, there was a significant increase in the serum mPL-II concentration after 24 and 48 h of fasting on day 12 and after 12, 36, and 48 h of fasting on day 15. Fasting significantly decreased the glucose and increased the FFA concentration of the serum at all fasting periods. Fasting had no effect on serum mPRL or mGH concentrations. In the second part of this study, pregnant mice were fasted for 24 h and then refed for an additional 24 h before being killed on day 12 of pregnancy. The changes in serum mPL-II, glucose, and FFA concentrations that occurred after a 24-h fast on day 12 of pregnancy were completely reversed by refeeding the animals for 24 h. Results from both studies indicate the involvement of mPL-II in the maternal response to fasting in pregnant mice.

Animals↗
PubMed1987

Nuclear morphometric analysis of osteoblast precursor cells in periodontal ligament, SL-3 rats.

Five small (55 days old, 196 +/- 5 g) (mean +/- SE) and five large (83 days old, 382 +/- 4 g) Sprague-Dawley strain, specific pathogen-free rats were exposed to a 7-day spaceflight and 12-h postflight recovery period. As measured in 3-micron sections, periodontal ligament (PDL) fibroblastlike cells were classified according to nuclear size: A + A' (40-79), B (80-119), C (120-169), and D (greater than or equal to 170 microns 3). Since the histogenesis sequence is A----A'----C----D----osteoblast, the relative incidence of A + A' to C + D is an osteogenic index. No difference in A + A' or C + D cells in small rats may reflect partial recovery of preosteoblast formation (A----C) during the 12-h postflight period. Large flight rats demonstrated increased numbers of A + A', indicating an inhibition of preosteoblast formation (A----C). At least in the older group, a 7-day flight is adequate to reduce PDL osteogenic potential (inhibition in PDL osteoblast differentiation and/or specific attrition of C + D cells) that does not recover by 12-h postflight.

Animals↗
PubMed1987

The lipolytic effects of mouse placental lactogen II, mouse prolactin, and mouse growth hormone on adipose tissue from virgin and pregnant mice.

The lipolytic activities of three structurally related mouse hormones, placental lactogen II (mPL-II), GH (mGH), and PRL (mPRL), and human PL (hPL) were investigated. Adipose tissue was obtained from virgin and day 12 and day 16 pregnant mice. Lipolytic activity was assessed by the ability of the hormones to stimulate glycerol release from fat explants in the presence of dexamethasone and by the ability of the hormones to sensitize adipose tissue to the lipolytic stimulus theophylline. In the first experiment, adipose tissue explants were incubated in Krebs-Ringer buffer with 0.0, 0.1, 0.5, 1.0, 5.0, and 10.0 micrograms/ml hormone for 4 h. mGH was lipolytic at a concentration of 0.5 micrograms/ml or greater in adipose tissue from both virgin and pregnant mice. mPRL was lipolytic at a concentration of 5.0 micrograms/ml or greater in adipose tissue from virgin mice. In adipose tissue from pregnant mice mPRL was not lipolytic in day 12 tissue, but it was lipolytic at a concentration of 5.0 micrograms/ml in day 16 tissue. mPL-II and hPL did not stimulate glycerol release in mouse adipose tissue from virgin or pregnant mice. In the second experiment preincubating adipose tissue from virgin mice in the presence of 0.5 or 5.0 micrograms/ml mGH significantly increased the ability of the tissue to respond to theophylline; however, mGH did not induce this response in adipose tissue from pregnant mice, mPRL, mPL-II, and hPL did not increase theophylline-induced lipolysis in adipose tissue from either virgin or pregnant mice. These results indicate that two lipolytic mechanisms are activated in adipose tissue from mice; mGH can activate both mechanisms, whereas mPRL can activate only one.

Adipose Tissue↗
PubMed1986

Osteoblast histogenesis in periodontal ligament and tibial metaphysis during simulated weightlessness.

According to nuclear size, fibroblast-like cells adjacent to bone surfaces in the periodontal ligament (PDL) and tibial primary spongiosa (PS) were classified as less differentiated progenitors and committed osteoprogenitors (A/A'), nonosteogenic cells (B), or preosteoblasts (C/D). The ratio of A/A' to C/D cells reflects osteogenic status of bone lining tissue. When 83-day-old rats were subjected to simulated weightlessness (S-W) for 17 d and examined for changes in osteoblast histogenesis, PDL and PS cell populations increased in A/A' cells (p less than 0.01; less than 0.05) but decreased in C/D cells (p less than 0.01; less than 0.05) compared to controls. These data indicate that the nuclear volume method, originally developed in PDL, can also be used to assess osteoblast histogenesis in PS of long bones, and that simulated weightlessness in the present experimental context interferes with osteoblast histogenesis. Since the surfaces of both weightbearing (PS) and nonweightbearing (PDL) bones were affected, systemic factors appear important in the gravity-related mechanism of osteoblast histogenesis. Although unloading of the tibia and cephalad fluid shifts occur during S-W, the data attained in this experiment could also be explained by stress and/or cessation of growth in the S-W rats.

Animals↗
PubMedDate not supplied

Characterization and hormonal regulation of granulosa cell-derived insulin-like growth factor binding protein-4.

OBJECTIVE: Because of the potential importance of insulin-like growth factor binding protein-4 (IGFBP-4) to ovarian physiology and the obvious limitations imposed by in vivo-exclusive experimental paradigms, we set out to delineate the characteristics and hormonal regulation of granulosa cell-derived IGFBP-4 under in vitro circumstances. METHODS: Granulosa cells obtained by follicular puncture of the ovaries from diethylstilbestrol-primed intact immature rats were subjected to culture for up to 72 hours. Insulin-like growth factor binding protein-4 mRNA extracted from culture was subjected to Northern blot hybridization. Data normalization was assured by reprobing with the hamster Chinese hamster ovary B (CHOB) cDNA, and the IGFBP-4/CHOB ratio was calculated. Conditioned culture media were subjected to Western ligand blot before and after immunoprecipitation with a rat IGFBP-4-directed polyclonal antiserum (alpha-B104). RESULTS: Immunoprecipitation studies revealed granulosa cell-derived IGFBP-4 to be composed of a major 24-kDa species as well as a relatively minor 27-kDa moiety. Given cultures of untreated granulosa cells from immature estrogen-treated rats, transcripts corresponding to IGFBP-4 displayed an initial temporary decline culminating in a 6-hour nadir (a decrease of 67%; P < .05) followed by relatively prompt recovery (within 24 hours) to levels comparable to those noted at the outset of the culture (time 0). However, additional (albeit statistically insignificant) increments were noted at the 48-hour (but not 72-hour) time point. Treatment of granulosa cells with increasing concentration of FSH resulted in decrements of up to 30% (P < .05) in the steady-state levels of IGFBP-4 transcripts. A modest, biphasic, time-dependent response was noted for IGFBP-4 transcripts after treatment with high-dose FSH (100 ng/mL), an effect characterized by 24- and 48-hour increments (51% [P < .05] and 26% [P = .052] over untrated controls, respectively) and a 72-hour decrement (25%; P = .16). The concurrent provision of the C19 aromatase substrate androstenedione (10(-7) mol/L) to the culture medium from 72 hours enhanced the inhibitory effect of FSH (100 ng/mL) for a maximal decrement in IGFBP-4 transcripts of 49% (P < .05). Treatment with insulin-like growth factor (IGF)-I produced limited inhibition (up to 26%) of the steady-state levels of IGFBP-4 transcripts (P < .05). CONCLUSION: Findings indicate the existence of heterogeneously-sized IGFBP-4 species, of which the 27-kDa (as distinct from the 24-kDa) IGFBP-4 moiety constitutes a relatively minor component. The steady-state levels of granulosa cell-derived IGFBP-4 transcripts display relatively limited regulation in response to treatment with either FSH or IGF-I.

Animals↗