Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0338671 (Steroids)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Human prostate tumor cells, LNCaP, contain androgen receptors and respond to androgens with increased growth rate. Although other steroid hormone receptors are not detectable in LNCaP cells, progesterone and estradiol stimulate the growth of these cells. The androgen receptor shows considerable cross binding activity with progesterone and estradiol but not with the glucocorticoid triamcinolone acetonide. The latter steroid does not have any effect on cell proliferation. LNCaP cells respond to epidermal growth factor (EGF) with an increased growth rate. Steroids that stimulate LNCaP cell proliferation also increase the number of EGF receptors per cell. In conclusion, LNCaP cells are sensitive to EGF. Different steroids bind to the androgen receptor and stimulate the proliferation of human prostate tumor cells. This stimulation of growth is preceded by an increase in EGF receptor number per cell.
 ...
PMID:Androgen receptor-mediated growth and epidermal growth factor receptor induction in the human prostate cell line LNCaP. 272 28

This study describes the effects of insulin, insulin-like growth factor 1 (IGF1), and epidermal growth factor (EGF) on the aromatase activity of granulosa cells isolated from immature rat ovaries. None of the growth factors alone influenced the basal level of aromatase activity, but did modulate follicle-stimulating hormone (FSH)-induced aromatase activity. Insulin and IGF1 augmented the action of a sub-optimal concentration of FSH (5 ng/mL) on aromatase activity in a dose-dependent manner. In contrast, EGF (1-10 ng/mL) was effective in inhibiting aromatase activity maximally stimulated by FSH. Since insulin and IGF1 had opposing actions to those of EGF on FSH-induced aromatase activity, we examined the interactions between the growth factors. EGF inhibited the actions of both FSH and insulin on aromatase activity. Both IGF1 and EGF increased the [3H]thymidine incorporation into the DNA of bovine granulosa cells in vitro, IGF1 being a more potent mitogen. Whereas EGF inhibited the actions of IGF1 on aromatase activity, it did not inhibit the effects of IGF1 on the growth of granulosa cells. In summary, growth factors influence both the differentiation and growth of granulosa cells, and may be important regulators of follicular development.
Steroids
PMID:Aromatase activity in granulosa cells: regulation by growth factors. 314 65

Infusions of isotopically labeled [3H] androstenedione with measurement of [3H] estrone in normal breast and breast tumor tissue have been carried out in an attempt to determine the contribution that aromatization makes to the estrogen content of breast tissues. After infusion of [3H] androstenedione for 12h there was significant uptake of this steroid by normal breast and breast tumors. [3H] Estrone was detected in all samples of normal breast tissue examined so far but not in all tumors. Aromatase activity when measured in vitro was found to be higher in breast tumors than in fat next to the tumor or normal breast fat. Studies in which we have examined the effect of epidermal growth factor on aromatase activity in cultured breast adipose tissue suggests that the response may be influenced by a subject's menopausal status. Results from these preliminary studies suggest that the aromatization of androgens may make a significant contribution towards the estrogen content of some breast tumors and that growth factors may also be involved in regulating aromatase activity.
Steroids
PMID:Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies. 350 63

Primary cultures of interstitial cells were prepared from the testis of mice, rats, and pigs. The cells were grown in a defined medium supplemented with low (0.1%) serum and insulin, transferrin and epidermal growth factor. Comparisons of the interstitial cell cultures from the three species were made for plating efficiency, cell survival, maintenance of hCG receptors and maintenance of steroidogenic responsiveness to hCG. The porcine cultures had a higher plating efficiency and higher hCG receptor levels per cell than Leydig cells from either rodent. Additionally, the porcine cells showed an increase in testosterone (T) production with hCG stimulation throughout their lifespan in culture while the rodent cultures showed a decrease in T stimulation with time with no stimulation by day 6 in culture. These data indicate that species differences exist in hCG receptor concentrations per cell, the maintenance of hCG receptors and steroidogenic response in culture. The initial high survival, purity and continued functional response of porcine interstitial cell cultures make them a superior system for the study of gonadotropin regulation of Leydig cell function.
Steroids 1981 Jul
PMID:Primary cultures of Leydig cells from rat, mouse and pig: advantages of porcine cells for the study of gonadotropin regulation of Leydig cell function. 627 Aug 52

Androgens stimulate the growth of prostatic carcinoma, possibly by modulating the activity of locally expressed growth factors. Recently, we have shown that an LHRH (or LHRH-like) system exerting an inhibitory action on cell proliferation is present in the human androgen-dependent prostatic tumor cell lines LNCaP. The following experiments have been performed in LNCaP cells to clarify whether LHRH might inhibit cell proliferation by interfering with the two major mitogenic factors for these cells: (a) testosterone (T), the major exogenous stimulating factor, and (b) epidermal growth factor (EGF), one of the locally produced growth factors. (a) It has been shown that an LHRH agonist (LHRH-A, Zoladex) counteracts the proliferative action of T in a dose-dependent way. To clarify whether LHRH might interfere with the activity of T in prostate tumors, LNCaP cells were treated with LHRH agonist over different time intervals, and the effects of treatment evaluated in terms of expression of androgen receptor mRNA. The data obtained indicate that LHRH-A does not affect androgen receptor expression at any time interval examined. (b) LHRH-A inhibits the mitogenic action of EGF on LNCaP cells and significantly reduces the concentration of EGF receptors in these cells. Experiments have been performed to explore whether LHRH-A might alter intracellular signaling mechanisms mediating the activity of EGF. In LNCaP cells LHRH-A blocks EGF-induced expression of the c-fos proto-oncogene but does not modify EGF-induced tyrosine phosphorylation of the EGF receptor. These data suggest that, in androgen-dependent prostate tumors, LHRH might inhibit cell proliferation by interfering with some but not all of the mechanisms mediating the mitogenic action of EGF. Possible interactions between LHRH and T-activated events still remain to be elucidated.
Steroids 1996 Apr
PMID:Growth factors in steroid-responsive prostatic tumor cells. 873 5

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

The rat adrenal cortex is composed of three zones: the zona glomerulosa, the zona fasciculata, and the zona reticularis. Several investigators have claimed the presence of a zona intermedia between the zonae glomerulosa and fasciculata. The cells of zona glomerulosa, a few layers of cells just beneath the adrenal capsule, synthesize and secrete aldosterone, whereas those of zonae fasciculata and reticularis secrete glucocorticoids and androgens, respectively. The function of the cells in zona intermedia is unclear, because they express neither aldosterone synthase nor 11 beta-hydroxylase. To investigate the mechanism underlying the zonal differentiation of adrenocortical steroidogenesis, attempts have been made to isolate and characterize zone-specifically expressed proteins such as steroidogenic enzymes and putative regulatory factors. Having subtracted the mRNAs present in the decapsulated adrenal gland from those in the adrenal capsule, we successfully isolated three distinct clones, each specifically expressed in the zona glomerulosa. One clone encoded a protein named zona glomerulosa-specific factor (ZOG), which had a putative signal peptide at the N-terminus, six tandem epidermal growth factor (EGF)-like repeats, and a transmembrane domain in the central portion and a short cytosolic stretch at the C-terminus. Immunohistochemical studies using the antibody raised against ZOG confirmed the presence of the protein in all layers of cells in the zona glomerulosa. In contrast, cells possessing aldosterone synthase were present only in the periphery of zona glomerulosa, just beneath the capsule. These findings suggest that there are at least two kinds of zona glomerulosa cells in the rat adrenal cortex, one expressing aldosterone synthase as well as ZOG, and another expressing only ZOG. The cells in the zona intermedia did not express ZOG, aldosterone synthase, or 11 beta-hydroxylase, but did express Ad4BP. ZOG was not detected in zonae fasciculata and reticularis where 11 beta-hydroxylase was present.
Steroids 1997 Jan
PMID:Zona glomerulosa-specific factor: cloning and function. 902 18

Both benign hyperplasia (BPH) and cancer of the prostate are manifest in men beyond the age of 50. Approximately 50% of men greater than 50 years of age will suffer from the symptoms associated with BPH, especially from bladder outlet obstruction. With the ever-increasing proportion of the population over 65 years of age worldwide, BPH is becoming an important medical problem as the world moves into the next millennium. Cancer of the prostate is the second most commonly diagnosed cancer after skin cancer in the male population of the United States, and the second most common cause of death from cancer after that of the lung. Overall, around the world the incidence of carcinoma of the prostate is increasing annually by 2-3%. Both race and geographical location have a profound influence of the prevalence of prostate cancer worldwide. Black men in the USA have the highest incidence, while the incidence is much lower in Asian men from China, Japan and Thailand. Although the prostate gland is androgen-dependent, it is now recognized that the biological actions of endocrine-related factors, such as androgens, oestrogens, glucocorticoids and certain dietary and environmental factors, are mediated within the gland by various growth regulatory factors. The growth regulatory factors such as epidermal growth factor (EGF), keratinocyte growth factors (KGF), fibroblast growth factors (FGFs) and insulin-like growth factors II and I are mitogenic and directly stimulate cell proliferation under the modulating influence of steroid hormones. Steroids are therefore essential but not directly responsible for cell proliferation. Certain plant compounds such as isoflavonoids, flavonoids and lignans have been proposed as cancer protective compounds in populations with low incidences of prostate diseases. In particular, soya contains the isoflavone genistein, a compound with many properties which could influence both endocrine and growth factor signalling pathways.
 ...
PMID:Phytoestrogens and diseases of the prostate gland. 1038 17


1 2 Next >>