Cytoskeletal Regulation of hCG-Induced Receptor Clustering in Transformed Leydig Cells

Maurer, David R.; Wimalasena, Jay; Indrapichate, Korakod; Puett, David; Majercik, Mary H.

doi:10.1159/000154773

Cited by 3 publications

(2 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies with transformed Leydig cells suggest that human CG (hCG) induces cytoskeleton-dependent receptor clustering, which appears to be a prereq uisite for steroidogenesis. 64,65 Our studies indicate that the primary effect of hCG on stromal fibroblasts is the induction of α-smodth muscle action (αSMA) 54,60 (Fig. 2F).…”

Section: Phase Ii-establishment Of Uterine Receptivity: Role Of Chorimentioning

confidence: 79%

Implantation in the Baboon: Endometrial Responses

et al. 1999

View full text Add to dashboard Cite

Blastocyst implantation in the baboon usually occurs between 8 and 10 days post ovulation. Changes that occur within this window of receptivity and immediately following implantation can be divided into three distinct phases. The first phase, regulated by estrogen and progesterone, is characterized primarily by changes in both the luminal and glandular epithelial cells in preparation for blastocyst apposition and attachment. The second phase is the further modulation of these steroid induced changes in both epithelial and stromal cells by embryonic signals. The final phase is associated with trophoblast invasion and the remodeling of the endometrial stromal compartment. During the initial phase, the actions of estrogen and progesterone are dependent on the presence of specific receptors. Estrogen up-regulates both its own receptor (ER) and the progesterone receptor (PR), while progesterone down-regulates this expression pattern. However, the pattern of progesterone-induced down-regulation of ER and PR is confined to the epithelial cells and demonstrates a gradient effect from the functionalis to the basalis. What is most intriguing is that the loss of epithelial PR is closely correlated with the establishment of uterine receptivity. Coincident with the changes in ER and PR expression, epithelial cells undergo alterations in their cytoskeletal architecture and secretory profile. These changes can be counteracted by PR antagonist treatment during the luteal phase. Although estrogen and progesterone play a critical role in establishing the initial phase of uterine receptivity, it is becoming increasingly evident that the embryo induces functional receptivity in ruminants and rodents. In our studies in the primate, we demonstrate that chorionic gonadotrophin when infused in a manner that mimics blastocyst transit, has physiological effects on the three major cell types in the uterine endometrium. The luminal epithelium undergoes endoreplication and distinct epithelial plaques are evident. The glandular epithelium responds by inducing transcriptional and post-translational modifications in the major secretory product, glycodelin. The stromal fibroblasts initiate their differentiation process into a decidual phenotype and are characterized by the expression of actin filaments. In phase three, blastocyst attachment to the surface epithelium and subsequent implantation is associated with local remodeling of the maternal stroma, smooth muscle, and endothelium of the blood vessels by the trophoblast. In addition, there is a gradual diminution of the epithelial plaques on the luminal surface although the glandular epithelium remains highly secretory. The most dramatic effect is on the stromal fibroblasts, which in response to embryonic stimuli, differentiate into decidual cells, the major cell type of the gestational endometrium. This differentiation is characterized by the expression of insulin-like growth factor binding protein-1 (IGFBP-1) in these cells. The cytokine IL-1 beta is one possible embryonic signal. COX-2 is t...

show abstract

Section: Phase Ii-establishment Of Uterine Receptivity: Role Of Chorimentioning

confidence: 79%

Implantation in the Baboon: Endometrial Responses

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Studies with transformed Leydig cells (MA10 cells) suggest that hCG induces cytoskeletal-dependent receptor clustering, which appears to be a prerequisite for steroidogenesis (34,35). In addition, rapid reorganization of the cytoskeleton is necessary for cellular motility and cell division (36,37).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the baboon ( Papio anubis ) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity

Fazleabas

Donnelly

Srinivasan

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

156

181

View full text Add to dashboard Cite

This study was undertaken to determine the modulation of uterine function by chorionic gonadotrophin (CG) in a nonhuman primate. Infusion of recombinant human CG (hCG) between days 6 and 10 post ovulation initiated the endoreplication of the uterine surface epithelium to form distinct epithelial plaques. These plaque cells stained intensely for cytokeratin and the proliferating cell nuclear antigen. The stromal fibroblasts below the epithelial plaques stained positively for ␣-smooth muscle actin (␣SMA). Expression of ␣SMA is associated with the initiation of decidualization in the baboon endometrium. Synthesis of the glandular secretory protein glycodelin, as assessed by Western blot analysis, was markedly up-regulated by hCG, and this increase was confirmed by immunocytochemistry, Northern blot analysis, and reverse transcriptase-PCR. To determine whether hCG directly modulated these uterine responses, we treated ovariectomized baboons sequentially with estradiol and progesterone to mimic the hormonal profile of the normal menstrual cycle. Infusion of hCG into the oviduct of steroidhormone-treated ovariectomized baboons induced the expression of ␣SMA in the stromal cells and glycodelin in the glandular epithelium. The epithelial plaque reaction, however, was not readily evident. These studies demonstrate a physiological effect of CG on the uterine endometrium in vivo and suggest that the primate blastocyst signal, like the blastocyst signals of other species, modulates the uterine environment prior to implantation.

show abstract

EFFECT OF Ni2+ ON THE TESTOSTERONE PRODUCTION OF MOUSE PRIMARY LEYDIG CELL CULTURE

L¹

1998

Journal of Toxicology and Environmental Health, Part A

View full text Add to dashboard Cite

This study evaluated the effects of Ni2 on testosterone (T) production of mouse Leydig cells in vitro following an in vivo or in vitro exposure. CFLP mice were subjected to repeated exposure (4 treatments, subcutaneously, every 3 d) to 10, 20 or 40 mg/kg body weight of NiSO4 or 1.0 ml of 0.9% NaCl solution. Depressed human chorionic gonadotropin (hCG)-stimulated T response was seen over a 48-h culture of testicular interstitial cells obtained from the animals exposed to 20 mg/kg or higher dose of NiSO4, while the basal T production remained unaltered. There were no Ni2+-related changes in the body weights or in the weights of testes, epididymides, adrenals, and kidneys. No histopathological alteration was found in the examined organs of NiSO4-treated groups except the dose-dependent tubular lesions in kidney as a result of a specific rather than a general cytotoxic action. To assess the direct effect of Ni2+ on Leydig-cell T production, testicular interstitial cells were cultured with Ni2+ (62.5 to 1000 microM) for 48 h in the presence or absence of maximally stimulating concentration of hCG. Dose-dependent depression in hCG-stimulated T production was seen at 125 microM or higher dose of Ni2+, while basal T production was unaffected. In order to evaluate the time dependency of this effect the cells were cultured for various times in the presence or absence of 250 and 1000 microM Ni2+. Decreased hCG-stimulated T production was found in the cultures maintained at least for 4 h in the presence of 1000 microM Ni2+, whereas at 250 microM at least 16 h was required to elicit the depression. Cell viability was assessed by a metabolic activity (MTT) assay. The viability of cells was unaltered by 250 microM Ni2+, and only a slight decrease was found even at the end of the 48-h culture period in the presence of 1000 microM Ni2+. Our results show a dose-related depression in stimulated T production of mouse Leydig cells in culture following either in vivo or in vitro Ni2+ treatment at a dose that does not induce any general toxic or significant cytotoxic action. The data of the time-course study indicate that the effect of Ni2+ on Leydig-cell T production is both time and concentration dependent, and not due to cytotoxicity.

show abstract

Cytoskeletal Regulation of hCG-Induced Receptor Clustering in Transformed Leydig Cells

Cited by 3 publications

References 29 publications

Implantation in the Baboon: Endometrial Responses

Implantation in the Baboon: Endometrial Responses

Modulation of the baboon ( Papio anubis ) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity

EFFECT OF Ni2+ ON THE TESTOSTERONE PRODUCTION OF MOUSE PRIMARY LEYDIG CELL CULTURE

Contact Info

Product

Resources

About