Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The adrenal gland of the human fetus (HFA) is relatively large compared to that of the adult and exhibits an extremely high rate of steroidogenesis both in vivo and in vitro. The fetal zone cells make up 80-85% of the volume of the HFA and are the major site of steroid production during fetal development. We have recently demonstrated that calcium is involved in the regulation of steroidogenesis in fetal zone cells of the HFA. There is considerable evidence that many actions of calcium within cells are mediated by the calcium-binding protein calmodulin. The purpose of the present investigation was to determine if calmodulin also plays a role in HFA steroidogenesis. To investigate this possibility, the fetal zone was dissected from fetal adrenals of first and second trimester human abortuses. After collagenase digestion of the tissue, dispersed fetal zone cells were maintained in a Krebs-Ringers medium at 37 C for a 3-h incubation. Cells were incubated with and without ACTH (10(-8) M) in the presence of the calmodulin inhibitors trifluoperazine (TFP), chlorpromazine (CPZ), and calmidazolium (CAL) at concentrations of 5-100 microM. The media were assayed for contents of dehydroepiandrosterone sulfate (DS), cortisol (F), pregnenolone, and cAMP by RIA. The addition of ACTH stimulated F secretion 5- to 10-fold compared to that in control fetal zone cells. DS secretion increased up to 5-fold and pregnenolone about 2-fold in the presence of ACTH compared to values in control cells. ACTH also stimulated cAMP secretion by 10-fold compared to that in control cells. The addition of TFP, CPZ, and CAL significantly inhibited ACTH-stimulated DS, F, and pregnenolone secretion in a dose-related fashion to near-control levels. We observed that TFP, CPZ, and CAL inhibited cAMP accumulation as well as Bu2cAMP-stimulated steroid secretion. The metabolism of 22R-hydroxycholesterol to pregnenolone was inhibited by TFP and CPZ, but not by CAL. These studies suggest that calmodulin plays a role in regulating steroidogenesis in fetal zone cells of the HFA.
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PMID:The role of calmodulin antagonists on steroidogenesis by fetal zone cells of the human fetal adrenal gland. 302 95

The morphological and steroidogenic properties of preparations of interstitial cells isolated by collagenase treatment from testes of immature and mature rats have been compared. After additional purification on a Ficoll gradient, 80% of cells from mature rat testes were found to be Leydig cells; 20% were macrophages. Forty to sixty per cent of collagenase-dispersed cells isolated from immature rats were Leydig cells, 37% were mesenchymal cells and there were no macrophages. A preparation in which 90% cells were Leydig cells could be obtained from immature testes after further purification by centrifugation through a Percoll gradient. The distribution of steroidogenic enzymes through the gradient corresponded to the distribution of LH-dependent steroid production. The results indicate that the steroidogenic activity per Leydig cell from mature rats is fourfold greater than the activity in immature rat Leydig cells in control incubations or after stimulation with LH, dibutyryl cyclic AMP or in the presence of 22R-hydroxycholesterol.
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PMID:Comparison of the cellular composition and steroidogenic properties of preparations of interstitial cells isolated from immature and mature rat testis. 355 48

In addition to the regulation of FSH secretion, it has been clearly shown that inhibin and activin have paracrine/autocrine effects in the gonads. We have studied the effect of human recombinant inhibin A and human recombinant activin A on immature porcine Leydig cells in vitro. Leydig cells were prepared by collagenase digestion of testes from 3-week-old piglets, purified on Percoll gradient, then cultured in a chemically defined medium. The cells were treated with increasing amounts of inhibin A or activin A (0.5-200 ng/ml). Direct application of either inhibin A or activin A on Leydig cells for 4 or 48 h did not stimulate basal testosterone secretion. Conversely, treatment of the cells for 48 h with either factor resulted in a dose-dependent increase in hCG-stimulated testosterone secretion (10[-9] M hCG, 2 h) with a maximal effect of 2.40 +/- 0.37- and 2.43 +/- 0.37-fold increases for inhibin A and activin A, respectively, and these changes were associated with a slight increase in LH/hCG-binding sites (1.37 +/- 0.19- and 1.24 +/- 0.11-fold increases). In addition, both inhibin A and activin A enhanced messenger RNA (mRNA) levels of LH/hCG receptor (2.75 +/- 0.40- and 2.53 +/- 0.60-fold increases) and cytochrome P450 17alpha-hydroxylase (6 +/- 1- and 3.5 +/- 0.6-fold increases), but had no effect on side-chain cleavage cytochrome P450 or cytochrome P450 aromatase mRNAs. 3beta-Hydroxysteroid dehydrogenase mRNA levels were increased (3.1 +/- 1.3-fold increase) by activin A, but not by inhibin A. However, inhibin A blocked the stimulatory action of activin A. In keeping with these changes in the steroidogenic enzyme mRNAs, both peptides enhanced the conversion of exogenous 22R-hydroxycholesterol and progesterone, but only activin A increased the conversion of dehydroepiandrosterone into testosterone. In conclusion, our findings demonstrate that both inhibin A and activin A have a stimulatory effect on immature porcine Leydig cell differentiated function in vitro. As inhibin has a stimulatory and activin has an inhibitory effect on rat Leydig cell function in vitro, the effects of these factors on Leydig cells seem to be species dependent.
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PMID:Stimulating effect of both human recombinant inhibin A and activin A on immature porcine Leydig cell functions in vitro. 934 6

The function of the adrenal cortex of the marmoset monkey Callithrix jacchus has been investigated. In common with other New World primates, these animals seem to be glucocorticoid resistant. Blood and adrenal glands were obtained from male and female animals under terminal pentobarbitone anesthesia. Dispersed adrenal cell preparations were obtained by treatment with collagenase and incubated with ACTH(1-24), (0.1-1000 nM) angiotensin II (0.1-1000 nM), dibutyryl cyclic AMP (dbcAMP; 30-1000 microM), and forskolin (FSK; 1-30 microM). Plasma cortisol levels (2113 +/- 449 ng/ml male; 3858 +/- 429 ng/ml female) were found to be 10- to 20-fold higher than those quoted for Old World primates and man. The cell preparations showed no significant response to any dose of ACTH tested (0.1-1000 nM), although addition of exogenous precursor (22R-hydroxycholesterol, 2.5 microM) resulted in an increased yield of cortisol and aldosterone. Cyclic AMP production was increased in response to forskolin (1-30 microM) but not ACTH(1-24) (1-1000 nM). In addition, dose-related responses to angiotensin II (maximal stimulation of 316 +/- 49% basal aldosterone at 100 nM angiotensin II), dbcAMP (maximal stimulation of 449 +/- 24% basal cortisol at 300 microM dbcAMP), and forskolin (maximal stimulation of 394 +/- 31% basal cortisol at 10 microM FSK) were obtained. The lack of a response in vitro to ACTH in C. jacchus cannot, therefore, be attributed either to general failure of the cells or to defects in postreceptor signaling mechanisms. The results suggest that there is a reduction in adrenal ACTH receptor number or affinity, with a high basal production rate in vivo maintaining the elevated plasma cortisol levels.
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PMID:Adrenocortical function in a new world primate, the marmoset monkey, Callithrix jacchus. 1104 5