The regulation of steroidogenesis is different in the two types of ovine luteal cells

1985 ◽  
Vol 63 (3) ◽  
pp. 240-248 ◽  
Author(s):  
P. B. Hoyer ◽  
G. D. Niswender
Keyword(s):  
Adenylate Cyclase ◽  
Cell Types ◽  
High Rate ◽  
Small Cells ◽  
Progesterone Secretion ◽  
Steroidogenic Cell ◽  
Luteal Tissue ◽  
Enhanced Secretion ◽  
Dependent Protein

Ovine luteal tissue contains two distinct steroidogenic cell types, small (8–20 μm) and large (>20 μm), which differ based on morphological and biochemical criteria. Unstimulated small cells secrete low levels of progesterone, respond to LH or dibutyryl cAMP (dbcAMP) with enhanced secretion of progesterone, and contain most of the receptors for LH. The unstimulated large cells, conversely, secrete high levels of progesterone, have few, if any, receptors for LH, and do not respond to LH –or dbcAMP with increased progesterone secretion. The lack of response to dbcAMP by large cells was investigated. Large cells incubated in the presence of cholesterol, ram serum, or 25-hydroxycholesterol did not demonstrate substrate limitation. Hormone-independent stimulation of adenylate cyclase by cholera toxin or forskolin resulted in increased adenylate cyclase activities (P < 0.01), cAMP accumulation (P < 0.05), and the binding of endogenous cAMP (P < 0.05) by type 1 cAMP-dependent protein kinase in both small and large cells. These treatments were accompanied by enhanced secretion of progesterone (P < 0.05) in small cells. In contrast, large cells did not respond with an increase in progesterone secretion under these conditions. These observations suggest that the high rate of secretion of progesterone in unstimulated large cells is not regulated by cAMP.

scholarly journals Role of Luteal Glucocorticoid Metabolism during Maternal Recognition of Pregnancy in Women

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5769-5779 ◽  
Author(s):  
Michelle Myers ◽  
M. Christy Lamont ◽  
Sander van den Driesche ◽  
Nirmala Mary ◽  
K. Joo Thong ◽  
...  
Keyword(s):  
Cell Activity ◽  
Tissue Remodeling ◽  
Cell Types ◽  
Endocrine Gland ◽  
Steroidogenic Cell ◽  
Luteal Tissue ◽  
Maternal Recognition Of Pregnancy

The human corpus luteum (hCL) is an active, transient, and dynamic endocrine gland. It will experience extensive tissue and vascular remodeling followed by 1) demise of the whole gland without any apparent scarring or 2) maintenance of structural and functional integrity dependent on conceptus-derived human chorionic gonadotropin (hCG). Because cortisol has well-characterized roles in tissue remodeling and repair, we hypothesized that it may have a role in controlling luteal dissolution during luteolysis and would be locally produced toward the end of the luteal cycle. Glucocorticoid-metabolizing enzymes [11β-hydroxysteroid dehydrogenase (11βHSD) types 1 and 2] and the glucocorticoid receptor (GR) were assessed in hCL and cultures of luteinized granulosa cells (LGC) using immunofluorescence and quantitative RT-PCR. Furthermore, the effect of cortisol on steroidogenic cell survival and fibroblast-like cell activity was explored in vitro. The hCL expressed 11βHSD isoenzymes in LGC and nuclear GR in several cell types. hCG up-regulated the expression and activity of 11βHSD type 1 (P &lt; 0.05) and down-regulated type 2 enzyme (P &lt; 0.05) in vitro and tended to do the same in vivo. Cortisol increased the survival of LGC treated with RU486 (P &lt; 0.05) and suppressed the activity of a proteolytic enzyme associated with luteolysis in fibroblast-like cells (P &lt; 0.05). Our results suggest that, rather than during luteolysis, it is luteal rescue with hCG that is associated with increased local cortisol generation by 11βHSD type 1. Locally generated cortisol may therefore act on the hCL through GR to have a luteotropic role in the regulation of luteal tissue remodeling during maternal recognition of pregnancy.

Luteotrophic factors in hyperstimulated pseudopregnant rabbit: II – High sensitivity to hCG of luteal tissue and small luteal cells

1997 ◽  
Vol 154 (2) ◽  
pp. 259-265 ◽  
Author(s):  
R K Arioua ◽  
A Benhaïm ◽  
C Féral ◽  
P Leymarie
Keyword(s):  
High Sensitivity ◽  
Chorionic Gonadotrophin ◽  
Small Cells ◽  
Corpora Lutea ◽  
Aromatase Activity ◽  
Large Contribution ◽  
Luteal Cells ◽  
Progesterone Secretion ◽  
Luteal Tissue

Abstract Previous studies on rabbit corpus luteum (CL) led to the conclusion that the luteotrophic complex, in rabbit, may include LH as well as oestradiol for normal luteal function. However, the requirement for LH is controversial. We have recently demonstrated the existence of a human chorionic gonadotrophin (hCG)-stimulated aromatase activity in cultured corpora lutea from a hyperstimulated pseudopregnant rabbit model, which develops a large number of corpora lutea, with only a few or no follicles in the ovaries. The present study was undertaken to investigate the in vitro responsiveness to hCG, dibutyryl cAMP (dbcAMP) and oestradiol of those corpora lutea. Pseudopregnancy (PP) was induced in rabbits by i.m. injection of 200 IU equine chorionic gonadotrophin daily for 2 days followed on day 4 by i.m. injection of 200 IU hCG (day 0 of PP). Luteal tissue and small and large luteal cells obtained at days 5 and 9 of PP were cultured for 24 h or during several days respectively with or without hCG, dbcAMP or oestradiol. Basal progesterone secretion was 3·6- and 22-fold higher in large cells compared with small ones at day 5 and 9 of PP respectively. When stimulated by small doses of hCG, luteal tissue responded by a 5-fold increase in progesterone secretion. Small cells produced four times higher amounts of progesterone than controls in the presence of 1 mIU/ml hCG and more than ten times in the presence of 0·1 IU/ml hCG, whereas large cells were insensitive to hCG stimulation. dbcAMP mimicked the effect of hCG on progesterone secretion by luteal tissue and luteal cells and oestradiol stimulated basal progesterone secretion in both small and large luteal cells. Given the large contribution of non stimulated large cells to luteal progesterone production and the remarkably high sensitivity of luteal tissue to gonadotrophin in vitro it seems that interactions between the two types of cells might occur during LH stimulation. Our results suggest that LH could participate in the luteotrophic complex at least in part through the stimulation of endogenous oestradiol production by luteal cells. Journal of Endocrinology (1997) 154, 259–265

scholarly journals Human Immunodeficiency Virus Type 1 Replication in the Absence of Integrase-Mediated DNA Recombination: Definition of Permissive and Nonpermissive T-Cell Lines

2001 ◽  
Vol 75 (17) ◽  
pp. 7944-7955 ◽  
Author(s):  
Noriko Nakajima ◽  
Richard Lu ◽  
Alan Engelman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Lines ◽  
Dna Recombination ◽  
Cell Types ◽  
Class Ii ◽  
Class I ◽  
Immunodeficiency Virus ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT Functional retroviral integrase protein is thought to be essential for productive viral replication. Yet, previous studies differed on the extent to which integrase mutant viruses expressed human immunodeficiency virus type 1 (HIV-1) genes from unintegrated DNA. Although one reason for this difference was that class II integrase mutations pleiotropically affected the viral life cycle, another reason apparently depended on the identity of the infected cell. Here, we analyzed integrase mutant viral infectivities in a variety of cell types. Single-round infectivity of class I integration-specific mutant HIV-1 ranged from <0.03 to 0.3% of that of the wild type (WT) across four different T-cell lines. Based on this approximately 10-fold influence of cell type on mutant gene expression, we examined class I and class II mutant replication kinetics in seven different cell lines and two primary cell types. Unexpectedly, some cell lines supported productive class I mutant viral replication under conditions that restricted class II mutant growth. Cells were defined as permissive, semipermissive, or nonpermissive based on their ability to support the continual passage of class I integration-defective HIV-1. Mutant infectivity in semipermissive and permissive cells as quantified by 50% tissue culture infectious doses, however, was only 0.0006 to 0.005% of that of WT. Since the frequencies of mutant DNA recombination in these lines ranged from 0.023 to <0.093% of the WT, we conclude that productive replication in the absence of integrase function most likely required the illegitimate integration of HIV-1 into host chromosomes by cellular DNA recombination enzymes.

Interpolation of microtubules into cortical arrays during cell elongation and differentiation in roots of Azolla pinnata

1979 ◽  
Vol 37 (1) ◽  
pp. 411-442
Author(s):  
A.R. Hardham ◽  
B.E. Gunning
Keyword(s):  
Cell Differentiation ◽  
Cell Walls ◽  
Unit Length ◽  
Cell Types ◽  
High Rate ◽  
Wall Thickening ◽  
Cortical Microtubules ◽  
Azolla Pinnata ◽  
Outer Cortex ◽  
Cortical Cells

Longitudinal sections of roots of Azolla pinnata R. Br. were prepared for electron microscopy so that cortical microtubules could be counted along the longitudinal walls in cell files in the endodermis, pericycle, and inner and outer cortex, and in sieve and xylem elements. With the exception of the xylem, where there are no transverse cell divisions, each file of cells commences with its initial cell and then possesses a zone of concomitant cell expansion and transverse cell division, followed, after completion of the divisions, by a zone of terminal cell differentiation. The cells augment their population of cortical microtubules as they elongate and divide, showing a net increase of up to 0.6 micron of polymerized microtubule length per min. Two main sub-processes were found: (i) When a longitudinal wall is first formed it is supplied with a higher number of microtubules per unit length of wall than it will have later, when it is being expanded. This initial quota becomes diluted as the second sub-process commences. (ii) The cells interpolate new microtubules at a rate which is characteristic of the cell, and, in the endodermis, of the face of the cell, while the cell elongates. Most cell types thus maintain a set density of cortical microtubules while they elongate and divide. Comparisons of endodermal cells in untreated controls, and roots that had been treated with colchicine, low temperature, or high pressure indicate that the initial quota of microtubules, and the later interpolations, and differentially sensitive to microtuble perturbations. Three types of behaviour, all related to changes in the cell walls, were noted as cortex, xylem and sieve element cells entered their respective phases of cell differentiation. The cortical cells expanded in all dimensions, and the interpolation of microtubules diminished or ceased. The sieve elements continued to elongate, and interpolated at a high rate, reaching unusually high densities of microtubules when the cell walls were being thickened. During this period a net increase of 2.0 micron of polymerized microtubule length per min was calculated. Thereafter interpolation ceased and the density of microtubules declined. The sample applied to developing xylem except that, because wall-thickening is localized rather than widespread, the rise and subsequent fall in the density of microtubules was less marked. The data are discussed in relation to the participation of microtubules in wall deposition and to the hypothesis that cortical microtubules arise in discrete zones along the edges of cells.

Six git genes encode a glucose-induced adenylate cyclase activation pathway in the fission yeast Schizosaccharomyces pombe

1993 ◽  
Vol 105 (4) ◽  
pp. 1095-1100 ◽  
Author(s):  
S.M. Byrne ◽  
C.S. Hoffman
Keyword(s):  
Adenylate Cyclase ◽  
Schizosaccharomyces Pombe ◽  
Glucose Repression ◽  
Signal Transduction Pathway ◽  
Activation Pathway ◽  
Cyclase Activation ◽  
Adenylate Cyclase Activation ◽  
Before And After ◽  
Dependent Protein ◽  
Camp Levels

An important eukaryotic signal transduction pathway involves the regulation of the effector enzyme adenylate cyclase, which produces the second messenger, cAMP. Previous genetic analyses demonstrated that glucose repression of transcription of the Schizosaccharomyces pombe fbp1 gene requires the function of adenylate cyclase, encoded by the git2 gene. As mutations in git2 and in six additional git genes are suppressed by exogenous cAMP, these ‘upstream’ git genes were proposed to act to produce a glucose-induced cAMP signal. We report here that assays of cAMP levels in wild-type and various mutant S. pombe cells, before and after exposure to glucose, show that this is the case. The data suggest that the cAMP signal results from the activation of adenylate cyclase. Therefore these ‘upstream’ git genes appear to encode a glucose-induced adenylate cyclase activation pathway. Assays of cAMP on a strain carrying a mutation in the git6 gene, which acts downstream of adenylate cyclase, indicate that git6 may function to feedback regulate adenylate cyclase activity. Thus git6 may encode a cAMP-dependent protein kinase.

Immunotherapy: Building a bridge to a cure for type 1 diabetes

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. 510-516
Author(s):  
Jeffrey A. Bluestone ◽  
Jane H. Buckner ◽  
Kevan C. Herold
Keyword(s):  
Type 1 Diabetes ◽  
Immune Cell ◽  
Cell Types ◽  
Underlying Disease ◽  
Β Cells ◽  
Current State ◽  
Islet Inflammation ◽  
Genetic And Environmental Factors ◽  
Key Events

Type 1 diabetes (T1D) is an autoimmune disease in which T cells attack and destroy the insulin-producing β cells in the pancreatic islets. Genetic and environmental factors increase T1D risk by compromising immune homeostasis. Although the discovery and use of insulin have transformed T1D treatment, insulin therapy does not change the underlying disease or fully prevent complications. Over the past two decades, research has identified multiple immune cell types and soluble factors that destroy insulin-producing β cells. These insights into disease pathogenesis have enabled the development of therapies to prevent and modify T1D. In this review, we highlight the key events that initiate and sustain pancreatic islet inflammation in T1D, the current state of the immunological therapies, and their advantages for the treatment of T1D.

scholarly journals Establishment of a Human Nonluteinized Granulosa Cell Line that Transitions from the Gonadotropin-Independent to the Gonadotropin-Dependent Status

Endocrinology ◽  
2012 ◽  
Vol 153 (6) ◽  
pp. 2851-2860 ◽  
Author(s):  
Bayasula ◽  
Akira Iwase ◽  
Tohru Kiyono ◽  
Sachiko Takikawa ◽  
Maki Goto ◽  
...  
Keyword(s):  
Cell Line ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Early Stage ◽  
Regulatory Protein ◽  
Cell Types ◽  
Mrna Levels ◽  
Steroidogenic Cell ◽  
Morphogenetic Protein ◽  
Steroidogenic Acute Regulatory

The ovary is a complex endocrine organ responsible for steroidogenesis and folliculogenesis. Follicles consist of oocytes and two primary steroidogenic cell types, the granulosa cells, and the theca cells. Immortalized human granulosa cells are essential for researching the mechanism of steroidogenesis and folliculogenesis. We obtained granulosa cells from a 35-yr-old female and immortalized them by lentivirus-mediated transfer of several genes so as to establish a human nonluteinized granulosa cell line (HGrC1). We subsequently characterized HGrC1 and investigated its steroidogenic performance. HGrC1 expressed enzymes related to steroidogenesis, such as steroidogenic acute regulatory protein, CYP11A, aromatase, and gonadotropin receptors. Stimulation with FSH increased the mRNA levels of aromatase, which consequently induced the aromatization of androstenedione to estradiol. Activin A increased the mRNA levels of the FSH receptor, which were synergistically up-regulated with FSH stimulation. HGrC1 also expressed a series of ligands and receptors belonging to the TGF-β superfamily. A Western blot analysis showed that bone morphogenetic protein (BMP)-4, BMP-6, and BMP-7 phosphorylated small mother against decapentaplegic (Smad)1/5/8, whereas growth differentiation factor-9 phosphorylated Smad2/3. BMP-15 and anti-Müllerian hormone phosphorylated Smad1/5/8 while also weakly phosphorylating Smad2/3. These results indicate that HGrC1 may possess the characteristics of granulosa cells belonging to follicles in the early stage. HGrC1 might also be capable of displaying the growth transition from a gonadotropin-independent status to gonadotropin-dependent one.

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