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Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of insulin and insulin-like growth factor-1 (IGF-1) on progesterone secretion by porcine granulosa cells and their modulatory effect on follicle-stimulating hormone (FSH)-induced responses were examined. For comparative purposes, growth hormone (GH), previously shown to stimulate IGF-1 secretion, was also included. Granulosa cells from ovarian follicles (3 to 5 mm) were cultured in multiwell plates for the first 48 hours, either in the presence or absence of 1% fetal bovine serum (FBS). Following plating, all cultures were maintained in serum-free media. The addition of only insulin, but not IGF-1 or GH, enhanced progesterone secretion under both culture conditions. When low-density lipoprotein was provided as steroid substrate, a stimulatory effect of insulin on progesterone accumulation was observed with a minimum dose of 10 ng/ml. Granulosa cells cultured in serum-free media from the time of plating secreted less progesterone and were less responsive to FSH compared with cultures plated with 1% FBS. Only insulin, but not IGF-1, enhanced FSH responses to threefold in cells cultured with 1% FBS. However, when cells were cultured in serum-free media from the time of plating, both insulin and IGF-1, but not GH, potentiated the responses to FSH, but insulin was more potent than IGF-1. Insulin-like growth-factor-1 binding studies with granulosa cells indicate the presence of specific high-affinity binding sites (Kd 3.96 nM). A dose of 100 ng/ml of insulin had negligible cross-reactivity with IGF-1 receptors.
Steroids 1990 Mar
PMID:Comparative effects of insulin and insulin-like growth factor-1 on follicle-stimulating hormone-induced responses in porcine granulosa cells. 215 94

Hyperinsulinism is associated with disorders of androgen production in humans. We have studied the effects of insulin and insulin-like growth factor-1 on androgen production in vitro using a crude preparation of mouse Leydig cells incubated with luteinizing hormone in a serum-free medium. We found a positive correlation between testosterone production and the luteinizing hormone dose over 3 hours. Exposure of the cells for 1 hour to insulin (1 micrograms/ml) prior to the addition of luteinizing hormone significantly augmented the amount of testosterone produced in response to the gonadotropin when added after this preincubation. In contrast, prior exposure of the cells to proinsulin (30 micrograms/ml), insulin-like growth factor-1 (30 ng/ml), or epidermal growth factor-1 (1 micrograms/ml) did not influence the testosterone response to luteinizing hormone. Transforming growth factor-beta reduced the testosterone response to luteinizing hormone. Transforming growth factor-beta (1,000 pg/ml) blocked the insulin augmentation of luteinizing hormone-stimulated testosterone production. We conclude that insulin has an endocrine effect on testosterone production by mouse Leydig cells in vitro. Furthermore, the Leydig cell response to insulin is itself sensitive to interaction with transforming growth factor-beta which may operate as part of the paracrine control of Leydig cell function.
Steroids 1990 Jun
PMID:Regulation of testicular function by insulin and transforming growth factor-beta. 220 Nov 4

Cellular regulation by hormones that utilize a myriad of intracellular signaling pathways is recognized to be quite complex. To investigate some of these effects in an established cell line, we tested a panel of hormones and modulators for their effects on cyclic AMP (cAMP) and progesterone production, both alone and in combination with human chorionic gonadotropin (hCG), using the MA-10 cultured Leydig tumor cell line. None significantly affected intracellular levels of cAMP, and only epidermal growth factor (EGF) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulated progesterone production. While EGF, basic fibroblast growth factor, insulin, insulin-like growth factor-1, and transforming growth factor beta all decreased cAMP production only, TPA decreased hCG-stimulated cAMP and progesterone production. Those factors that stimulated progesterone production also induced a characteristic morphological change ("rounding") of these cells. In addition, EGF, insulin, and TPA, like hCG, elevated mRNA levels of competence oncogenes (c-fos and c-myc), albeit to different extents. These data demonstrate the wide range of hormones to which the cultured Leydig tumor cell will respond, as well as the varying degree of responses observed in the intracellular signaling pathways that we examined.
Steroids 1989 Dec
PMID:Effects of hormones and intracellular mediators on differentiated functions of cultured Leydig tumor cells. 255 32

The effects of growth hormone (GH) +/- pregnant mare's serum gonadotropin (PMSG) on levels of insulin-like growth factor (IGF)-I and -II and IGF binding protein (BP)-2 and -3 in serum and follicular fluid (FFI) and on the expression of their mRNA in the ovaries of prepubertal gilts were determined. Steroids in FFI were also quantified. In the first experiment, GH, given for either 20 or 40 days, caused a distinct (threefold, p < 0.05) increase in IGF-I in both serum and FFI with no change in the FFI:serum ratio (0.65). Effects of GH on IGF-II were opposite, with a drop in circulating and FFI levels (p < 0.05). In contrast to data for IGF-I, FFI levels were higher than those in serum for IGF-II (1.42, FFI:serum); IGF-II levels and the ratio fell after GH treatment. GH for either 20 days or 40 days increased serum IGBP-3 to 140% and 250% of control values while decreasing serum IGFBP-2 by 46% and 31%, respectively (p < 0.001). FFI IGFBP-3 was increased to a similar extent by GH (p < 0.005), but IGFBP-2 was not affected. Neither progesterone (P4) nor estradiol (E2) was affected by treatment with GH. However, androstenedione (A4) was decreased by 20-day and 40-day GH treatment relative to the respective controls (p < 0.05). In the second experiment, PMSG resulted in a modest (28%) increase in intrafollicular IGF-I (p < 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of growth hormone and gonadotropin on the insulin-like growth factor system in the porcine ovary. 750 57

Short-term lower leg growth, the insulin-like growth factor axis, and collagen turnover were assessed in 16 adolescents with asthma during treatment with inhaled budesonide, 800 micrograms/d, from a pressurized metered dose inhaler with a volume spacer. The design was a randomized double blind, placebo-controlled two-period crossover trial with treatment periods of 4 weeks and a 1-week wash-out. Lower leg growth was assessed by knemometry. Serum levels of insulin-like growth factor-I, insulin-like growth factor-binding protein-3, and the following markers of collagen turnover were evaluated: Serum markers of type I collagen formation and degradation; the carboxy-terminal propeptide of type I procollagen and the carboxy terminal pyridinoline cross-linked telopeptide of type I procollagen (ICTP), the serum marker of type III collagen formation; the amino-terminal propeptide of type III procollagen (PIIINP) and the urinary concentrations of the type I collagen degradation products pyridinoline (PYD) and deoxypyridinoline (DPD) cross-links. Mean lower leg growth velocity was suppressed from 0.51 mm/week during placebo to 0.18 mm/week during budesonide treatment (p < 0.001). No statistically significant effects on insulin-like growth factor-1, insulin-like growth faster-binding protein-3, or carboxy-terminal propeptide of type I procollagen were observed. ICTP and PIIINP were reduced with 2.3 and 2.5 micrograms/liter (p < 0.001 and p < 0.001, respectively) during budesonide treatment, urinary concentrations of PYD and DPD with 32.9 nmol/mmol creatinine (p < 0.005) and 6.8 nmol/mmol creatinine (p < 0.005), respectively. Significant correlations between lower leg growth velocity and ICTP, PIIINP, PYD, and DPD during placebo (p < 0.01, p < 0.05, p < 0.01, and p < 0.01) and budesonide (p < 0.05, p < 0.05, p < 0.05, and p < 0.05) periods were found. Short term lower leg growth suppression in adolescents treated with inhaled budesonide, 800 micrograms/d, reflects suppression of type I and III collagen turnover.
Steroids 1997 Oct
PMID:Short-term growth and collagen turnover in asthmatic adolescents treated with the inhaled glucocorticoid budesonide. 938 13

Growth hormone (GH), insulin-like growth factor (IGF-I), and prolactin (PRL) can influence various aspects of reproductive functions in both females and males. However, the physiological role of PRL and the GH-IGF-I axis in the control of reproduction has been difficult to define, and the recent availability of knock-out (KO) animals allows re-examination of this issue. PRL-receptor (R)-KO and PRL-KO females are sterile because of luteal failure. In addition, these mice have severe deficits in the development of oocytes and early embryos. However, male fertility is not affected in the PRL-KO and in most of the PRL-R-KO animals. IGF-KO animals have an infantile reproductive system and are sterile. GH-R-KO mice can reproduce, but their breeding performance is reduced, particularly in females. These data indicate that IGF-I signaling is required for normal reproductive development and confirm the requirement for PRL for fertility in the female mouse. GH resistance leads to quantitative deficits in reproductive development and functions, but does not preclude fertility in either sex. We suspect that PRL and the GH-IGF-I axis provide partially overlapping (redundant) regulatory inputs to the hypothalamic-pituitary-gonadal axis, and consequently, targeted disruption of either signaling pathway has relatively mild consequences on many functions related to reproduction. Overexpression of heterologous or homologous GH in transgenic animals can lead to severe reproductive deficits, including female sterility in some of the lines. Studies in GH transgenics should allow the identification of mechanisms that mediate the effects of chronic overexposure to GH on reproduction.
Steroids 1999 Sep
PMID:Role of growth hormone and prolactin in the control of reproduction: what are we learning from transgenic and knock-out animals? 1050 15

Although the growth promoting actions of relaxin on the reproductive tract have been well documented, the means by which relaxin stimulates reproductive tissue growth has not been identified. This report is an overview of studies from our laboratory investigating the role of the insulin-like growth factor (IGF) system in relaxin-induced growth of ovarian and uterine tissues. In the pig ovary, concentrations of relaxin that promote both theca and granulosa cell (GC) DNA synthesis in vitro also significantly (P < 0.05) increased GC IGF-I secretion. When IGF-I activity was blocked in the presence of an IGF-I antibody, the trophic effects of relaxin on GC [3H]thymidine incorporation into DNA were inhibited. However, there was no effect of relaxin on GC IGF binding proteins or IGF-I receptor. In the uterus, in vivo relaxin administration to prepubertal pigs resulted in the stimulation of growth and increases in uterine luminal IGF-I, IGF-II, and IGF binding proteins-2 and -3 secretion (P < 0.05). Thus, the trophic effects of relaxin on ovarian granulosa cells and the uterus involve tissue-specific changes in the IGF system. Additional studies are necessary to better understand the contribution of relaxin to follicular growth and uterine accommodation. These include characterization of the relaxin receptor and post-receptor binding events, as well as the potential impact of relaxin on other growth factor systems and how these systems interact to ultimately drive reproductive tissue growth.
Steroids 1999 Sep
PMID:Trophic effects of relaxin on reproductive tissue: role of the IGF system. 1050 21

Pharmacological doses of glucocorticosteroids given chronically are associated with a variety of negative side effects which impact the prolonged use of these potent anti-inflammatory agents. They have catabolic effects on protein, resulting in poor tissue healing, an increased incidence of infections and accelerated bone loss. Insulin resistance to both hepatic and peripheral tissues is a common consequence of chronic steroid use, leading at times to impaired carbohydrate metabolism. Steroids affect both the release and the effects of growth hormone (GH) at the target sites, hence becoming functional GH antagonists. When administered to growing children the side effects of glucocorticosteroid treatment are further compounded by a potent and significant suppression of linear growth. Ample experimental and clinical data support a role for GH therapy in counteracting some of the effects of glucocorticosteroids. Using isotope dilution methods we have previously shown that both GH and insulin-like growth factor (IGF)-I can decrease the protein wasting effects of prednisone administration in man. IGF-I has also been shown to enhance type I collagen formation in hydrocortisone-treated human osteoblasts. GH (through IGF-I) significantly enhances linear growth; thus, in states of "functional" GH deficiency, such as that observed in chronic steroid use, GH may also have a potentially beneficial effect. Studies in children on chronic prednisone doses with cystic fibrosis, chronic renal failure or juvenile rheumatoid arthritis have all shown beneficial effects on linear growth after prolonged GH therapy. Data from a recent study of ours using GH in children with steroid-dependent inflammatory bowel disease showed that GH treatment was associated with increased lean body mass, decreased adiposity and increased linear growth. Marked increases in IGF-I concentrations and in kinetic measures of bone calcium accretion (using calcium tracers) were also observed, without any deterioration of disease activity scores or carbohydrate tolerance. In conclusion, GH therapy may play a role in the treatment of children on chronic steroids both as a growth promoting agent and as an anabolic agent on whole body protein and bone. Longer term studies will be needed to better define the safety and efficacy of this approach.
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PMID:Growth hormone therapy in the glucocorticosteroid-dependent child: metabolic and linear growth effects. 1178 79

The estrogen receptor alpha (ERalpha) exists as a functional receptor at the plasma membrane. The structural requirements for localization and function are not well understood. Several laboratories have recently elucidated certain requirements. We recently found the translocation of ERalpha to the membrane in the absence of estrogen is dependent on caveolin-1 and serine 522 of the ERalpha protein. Mutation of serine 522 to alanine results in a 62% decrease in membrane localization and association with caveolin-1. Similarly, deletion of the caveolin-1 scaffolding domain (amino acids 60-100) largely prevents the localization of ERalpha at the plasma membrane. In the presence of estradiol (E2), ERalpha, Src-homology and collagen homology (Shc), and insulin-like growth factor receptor-1 proteins associate with and increase the localization of ERalpha at the membrane. Membrane-localized ERalpha functions as an atypical G-protein coupled receptor. There is no good evidence that ERalpha spans the membrane or contains an extracellular domain. E2/ERalpha activates different G-proteins in cell context-related fashion. These G-proteins lead to the activation of Src through PLC, PKC, IP3 and calcium influx. In breast cancer, Src activates matrix metalloproteinase-2 and -9, which cleaves heparin binding epidermal growth factor, and thus activates EGFR. This leads to downstream signaling through ERK and PI3 kinase, imparting cell growth and survival.
Steroids
PMID:Requirements for estrogen receptor alpha membrane localization and function. 1586 18

The hormonal response of 32 older men (70-80years) to a bout of sub-maximum aerobic exercise was examined before, after 16weeks of resistance or aerobic training and again after 4weeks of detraining. Blood samples were obtained at rest and immediately post sub-maximum exercise (30min @ 70% VO(2) max) to determine the concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone (Test), sex hormone-binding globulin (SHBG) and the calculation of free testosterone (FT). Both training groups had significant increases in leg strength and VO(2) max after 16weeks training but leg strength and VO(2) max returned to pre-training levels in the aerobic training and resistance training groups, respectively. During the 20week study there was no change in resting concentrations of any hormones among the three groups. There was no increase in GH, IGF-1 or SHBG immediately post sub-maximum exercise in any of the groups before training, after 16weeks training or after 4weeks detraining. Testosterone and FT increased immediately post sub-maximum exercise within all groups before training, after 16weeks training and after 4weeks detraining with the increase in Test and FT higher after 16weeks of resistance training compared to before training and after 4weeks detraining within the resistance training group. The increased responsiveness of Test and FT after 16weeks of resistance training was lost after 4weeks of detraining. Our results indicate that some physiological and hormonal adaptations gained after 16weeks training are lost after only 4weeks detraining.
Steroids 2012 Apr
PMID:The hormonal response of older men to sub-maximum aerobic exercise: the effect of training and detraining. 2224 72


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