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

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

Development of the human fetal adrenals is characterized by rapid growth and high levels of steroidogenic activity during the latter two-thirds of pregnancy. By midgestation, the human fetal adrenals are composed of two distinct cortical zones: the predominant fetal zone, which occupies 80-90% of the cortical volume and produces large amounts of the delta 5-steroid dehydroepiandrosterone sulfate, and the narrow definitive zone, which surrounds the fetal zone. Late in gestation, the peripheral portion of the fetal zone develops into a third, functionally distinct compartment, the transitional zone, which is the likely site of cortisol synthesis. Soon after birth, the adrenal cortex is remodeled and the fetal zone disappears. The adult cortical zones are thought to arise from the definitive zone, which persists postnatally. Development of the human fetal adrenals is regulated primarily by corticortropin (ACTH) secreted from the fetal pituitary. However, as ACTH is not a mitogen per se, its proliferative actions on human fetal adrenal cortical cells are thought to be mediated by autocrine/paracrine growth factors produced by adrenal cortical cells in response to ACTH. In addition, these growth factors appear to modulate the functional response of fetal adrenal cortical cells to ACTH. The roles of several growth factors, including the insulin like growth factors I and II (IGF-I and IGF-II), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), activin, inhibin, and the transforming growth factors alpha and beta (TGF-alpha and TGF-beta) have been examined. In cultured human fetal adrenal cortical cells, EGF, bFGF, and IGF-I and -II are mitogenic, whereas activin and TGF-beta inhibit proliferation. IGF-II, activin, and TGF-beta also modulate ACTH-stimulated steroidogenesis. Human fetal adrenal cortical cells express IGF-II, bFGF and the activin/inhibin subunits, and the abundance of mRNAs for each of these factors is up-regulated by ACTH, suggesting that these growth factors are autocrine/paracrine mediators of ACTH action. Thus, although human adrenal development is primarily regulated by ACTH, its actions appear to be mediated/modulated by a cohort of locally expressed growth factors, the net effect of which results in the unique growth and steroidogenic activity of the human fetal adrenal cortex.
Steroids 1997 Jan
PMID:Role of growth factors in the developmental regulation of the human fetal adrenal cortex. 902 17

Insulin and the insulin-like growth factors (IGFs) have multiple role in gene expression in steroidogenic cells. We investigated the regulation of steroidogenic enzyme gene expression by insulin and IGF-I in primary cultures of human adrenocortical cells from donors of ages 19-77 years. The effects of insulin and IGF-I observed here were independent of age and sex of the donor. After 5 days in serum-containing medium, cultures were exposed to insulin or IGF-I together with cyclic AMP analogs or ACTH in serum-free defined medium. Insulin and IGF-I at physiological concentrations increased mRNA levels for 17 alpha-hydroxylase and type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the absence of cyclic AMP or ACTH. They had lesser effects on 21-hydroxylase and cholesterol side-chain cleavage enzyme mRNA levels and were3 without effect on 11 beta-hydroxylase mRNA. All steroidogenic enzyme mRNAs were strongly increased by cyclic AMP or ACTH, and this increase was potentiated by insulin or IGF-I. These effects of insulin and IGF-I were accompanied by decreases in the ratio of dehydroepiandrosterone/cortisol synthesized from pregnenolone by the cultures. Induction of steroidogenic enzyme genes in adult human adrenocortical cells by insulin and IGF-I is unlikely to occur by means of a cyclic AMP-dependent mechanism. These data increase the evidence for an important regulation of steroidogenesis by these hormones.
Steroids 1997 Feb
PMID:Induction of steroidogenic enzyme genes by insulin and IGF-I in cultured adult human adrenocortical cells. 905 86

High doses of lipopolysaccharide (LPS) induce transient hyperglycemia, then chronic hypoglycemia and increased insulin resistance. In addition, appetite is reduced, while body temperature and concentrations of cortisol and tumor necrosis factor alpha (TNFalpha) are elevated. Furthermore, concentrations of GH and IGF-I are reduced in cattle. The objectives of this study were to determine whether a gonadal steroid implant (20 mg estrogen and 200 mg progesterone) given to endotoxemic steers would: (1) reduce hyperglycemia, reduce hypoglycemia, reduce insulin resistance, (2) reduce changes in concentrations of GH and IGF-I, (3) reduce inappetence and reduce concentrations of blood urea nitrogen (BUN) and non-esterified fatty acids (NEFA), and (4) reduce fever and concentrations of TNFalpha and cortisol. Holstein steers were assigned within a 2x2 factorial arrangement of treatments as follows (n=5 per group): C/C, no steroid and vehicle; S/C, steroid and vehicle; C/E, no steroid and LPS (1 microg/kg body weight (BW), i.v.); S/E, steroid and endotoxin. Steroid implants were given at 20 weeks of age (day 0) and serial blood samples (15 min) were collected on day 14 for 8 h, with vehicle or LPS injected after 2 h. Intravenous glucose tolerance tests (100 mg/kg BW) were carried out at 6 h and 24 h. Hyperglycemia was 67% lower (P<0.05) in S/E- compared with C/E-treated steers between 30 and 150 min after i.v. injection of LPS. Hypoglycemia developed after 4 h and insulin resistance was greater in S/E- compared with C/E-treated steers (P<0. 05) at 6 and 24 h. Concentrations of IGF-I were restored earlier in steroid-treated steers than in controls. Concentrations of GH were not affected by steroids, but increased 1 h after injection of LPS, then were reduced for 2 h. Appetite was greater (P<0.05) in S/E- (2.1% BW) compared with C/E-treated steers (1.1% BW) (pooled s.e.m.=0.3). Concentrations of NEFA increased after injecting LPS, but concentrations were lower (P<0.05) in S/E- compared with C/E-treated steers. LPS did not affect concentrations of BUN, but concentrations were lower in steroid-treated steers. Steroids did not affect body temperature or concentrations of TNFalpha and cortisol. In summary, gonadal steroids reduce hyperglycemia, reduce inappetence and tissue wasting, but increase insulin resistance. Furthermore, concentrations of IGF-I are restored earlier in steroid-treated than in non-steroid-treated steers injected with LPS. It is concluded that gonadal steroids reduce severity of some endocrine and metabolic parameters associated with endotoxemia. However, it is unlikely that gonadal steroids acted via anti-inflammatory and immunosuppressive actions of glucocorticoids or through reducing concentrations of cytokines.
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PMID:Estradiol/progesterone implants increase food intake, reduce hyperglycemia and increase insulin resistance in endotoxic steers. 983 64

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

Induction of apoptosis is a feature of the anti-tumor effects of certain vitamin D analogs. The aim of this study was to identify if common effectors are involved in cell death mediated by serum starvation, vitamin D analogs and tumor necrosis factor (TNF) alpha in 3 human breast cancer cell lines: MCF-7, T47-D and Hs578T. Incubation of cells in serum-free medium induced apoptosis as assessed by loss of cell viability and increased DNA fragmentation. Addition of IGF-I (30 ng/ml) protected against loss of cell viability in MCF-7 cells and co-treatment with two synthetic analogs (CB1093 and EB1089, 50 nM for 4 days) prevented these anti-apoptotic effects of IGF-I. Pretreatment of MCF-7 and Hs578T cells with the vitamin D analogs substantially potentiated the cytotoxic effects of TNFalpha. This cytokine was not cytotoxic for T47-D cells but co-incubation with CB1093 led to loss of cell viability. Potentiation by CB1093 of TNFalpha-induced apoptosis in MCF-7 cells was accompanied by increased activation of cytosolic phospholipase A2 and arachidonic acid release, which was partially inhibited by AACOCF3, a specific cPLA2 inhibitor. The broad-spectrum caspase inhibitor z-VAD-fmk prevented TNFalpha but not CB1093 mediated cell death and activation of cPLA2. Serum starvation induced apoptosis was accompanied by cPLA2 activation, which was inhibited by IGF-I and by z-VAD-fmk. However, the ability of these agents to suppress cPLA2 activation was abrogated by co-treatment with CB1093, suggesting a role for arachidonic acid release in the caspase-independent mechanism by which vitamin D analogs prevent the protective effects of IGF-I on breast cancer cell survival.
Steroids
PMID:Interaction of vitamin D analogs with signaling pathways leading to active cell death in breast cancer cells. 1117 39

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

It is now evident that the use of levonorgestrel-releasing intrauterine system (LNg-IUS) is effective for long-term management of menorrhagic women with uterine myomas because of a striking reduction in menorrhagia. This prompted us to characterize the effects of progesterone (P4) on the growth and apoptosis of uterine leiomyoma cells. On the other hand, we have recently noted that epidermal growth factor (EGF) and IGF-I play a crucial role in prompting uterine leiomyoma growth through stimulating the proliferative potential and inhibiting apoptosis of cultured human leiomyoma cells. In the present review, attention was paid to evaluate the effects of P4 on the expression of growth factors (EGF, IGF-I) and apoptosis-related factors (TNFalpha, Bcl-2 protein) in cultured uterine leiomyoma cells. Treatment with P4 augmented EGF and Bcl-2 protein expression, but inhibited IGF-I and TNFalpha expression in cultured leiomyoma cells. It is known that TNFalpha induces apoptosis in a variety of cell types and Bcl-2 protein is an apoptosis-inhibiting gene product. Thus, the results obtained suggest that P4 has dual actions on uterine leiomyoma growth: one is to stimulate leiomyoma cell growth and survival through up-regulating EGF and Bcl-2 protein expression as well as down-regulating TNFalpha expression in those cells, and the other is to inhibit leiomyoma cell growth through down-regulating IGF-I expression in those cells. This may explain why the size of uterine myomas during use of LNg-IUS increases in some but decreases in other instances. This may also explain why the size of uterine myomas during pregnancy does not increase despite the overwhelming increase in circulating concentrations of sex steroid hormones.
Steroids 2003 Nov
PMID:Effects of progesterone on growth factor expression in human uterine leiomyoma. 1466 73

Cervical softening is crucial for a normal parturition and corresponds to remodeling of the dominating cervical extra cellular matrix (ECM). The onset of labor as well as cervical ripening is under hormonal control. To get further information about the endocrine regulation of term cervical ripening the following study was undertaken: cervical biopsies were obtained vaginally at elective caesareans, after normal vaginal delivery and after PGE2 or antiprogestin RU486. Biopsies from non-pregnant women served as controls. The concentrations of estrogen receptor (ER) and progesterone receptor (PR) protein were quantitated by EIA and the mRNA levels by solution hybridization. The ERalpha and beta were localized by immunohistochemistry, identified by RT-PCR and quantitated by solution hybridization. The co-localizations of CD45 (leukocyte antigen) and CD68 (macrophage antigen) were studied by immunohistochemistry. The cervical concentrations of ER and PR proteins decreased at term to 15 and 25%, respectively, compared to the non-pregnant levels. A further decrease was measured in the maximal ripened cervix at parturition. The mRNA levels were unchanged but IGF-I mRNA reached a maximum at term. ERalpha mRNA was significantly decreased until delivery, whereas ERbeta mRNA, like IGF-I; was maximum at term. By immunostaining ERbeta could be co-localized with CD45 leukocyte antigen and CD68 macrophage specific antigen. Oral administration of RU486 induced a significant increase in ER protein concentration, whereas PGE2 and spontaneous ripening did not. These findings indicate that cervical ripening is related to significant local hormonal changes.
Steroids 2003 Nov
PMID:Endocrine regulation of cervical ripening in humans--potential roles for gonadal steroids and insulin-like growth factor-I. 1466 76


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