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Biomedical subjects

M R Caudle

Publications and source records attributed to M R Caudle.

At least 19 recordsLinked to original sources
PubMed1996

Is irregular regression of corpora lutea in climacteric women caused by age-induced alterations in the "tissue control system"?

PROBLEM: We have recently observed that the regression of corpora lutea (CL) in women during the reproductive period of life is accompanied by a diminution of Thy-1 differentiation protein release from vascular pericytes and an accumulation of T lymphocytes and activated macrophages among both degenerating granulosa lutein cells (GLC) and theca lutein cells. These data suggest that the immune system and other stromal factors, representing components of the "tissue control system," may play a role in regression of the CL. We investigated degenerating CL from climacteric women to address the possibility that the decline of immune functions with advancing age may result in incomplete regression of luteal tissue. This could contribute to the altered hormonal profiles and abnormal uterine bleeding that frequently occur during the climacteric. METHOD: Immunoperoxidase staining and image analysis were used to localize Thy-1 differentiation protein of vascular pericytes, cytokeratin staining of GLC, neural cell adhesion molecule expression by theca lutein cells, CD15 of neutrophils, CD4, CD14, CD68, and leukocyte common antigens of macrophages, and CD3 and CD8 determinants of T lymphocytes. We also investigated the expression of luteinizing hormone receptor (LH receptor) and mitogen activated protein kinases (MAP kinases) in luteal cells. Samples of regressing luteal tissue were obtained during the follicular phase from perimenopausal women (age 45-50) who exhibited prolonged or irregular cycles. For comparison, luteal tissues from women with regular cycles (age 29-45) and CL of pregnancy were also investigated. RESULTS: Corpora lutea of the climacteric women exhibited irregular regression of luteal tissue characterized by a lack of cytoplasmic vacuolization and nuclear pyknosis in GLC, and by a persistence of theca lutein cells exhibiting hyperplasia and adjacent theca externa layers. This was accompanied by a continuing release of Thy-1 differentiation protein from vascular pericytes. Persisting GLC lacked surface expression of macrophage markers (CD4, CD14, CD68 and leukocyte common antigen) as well as nuclear granules exhibiting CD15 of neutrophils, detected in regularly regressing GLC. In addition, such persisting GLC showed weak or no LH receptor expression, and retained the expression of cytokeratin. They also exhibited enhanced staining for MAP kinases. Strong cytoplasmic MAP kinase expression with occasional nuclear translocation was also detected in persisting theca lutein cells, indicating high metabolic activity of these cells. T lymphocytes, although occasionally present in luteal stroma within luteal convolutions, did not invade among persisting GLC and were virtually absent from layers of theca externa and theca lutein cells. CONCLUSIONS: These data indicate that the regressing CL in climacteric women may exhibit persistence of luteal cells, perhaps because of age-induced alterations of the immune system and other local stromal homeostatic mechanisms involved in the elimination of luteal cells. Persisting GLC and/or theca lutein cells may exhibit abnormal hormonal secretion that contributes to the alteration of target tissues, such as the endometrium, resulting in abnormal uterine bleeding, hyperplasia, and neoplasia.

Adult↗
PubMed1996

Vascular endothelial growth factor expression in cycling human endometrium.

OBJECTIVE: To determine the spatial distribution of vascular endothelial growth factor protein in human endometrium and to assess temporal fluctuations in vascular endothelial growth factor gene expression and variant isoform production by stromal and epithelial cells during the menstrual cycle. DESIGN: Prospective study design. PATIENTS: Early proliferative endometrial biopsies were obtained from women undergoing gynecologic surgery for benign conditions; secretory stage biopsies were obtained from patients undergoing routine infertility investigations without evidence of luteal insufficiency. MAIN OUTCOME MEASURE: Immunohistochemical detection of vascular endothelial growth factor protein in endometrial biopsies, analyses of vascular endothelial growth factor RNA expression, and isoform production in intact endometrium and isolated endometrial stromal and epithelial cells. RESULTS: Strong vascular endothelial growth factor immunoreactivity was detected in the glandular epithelial cells of the secretory endometrium with no discernible immunoreactivity in stroma cells. The proliferative endometrium demonstrated prominent glandular immunoreactivity and faint, inconsistent stromal cell immunoreactivity. Preincubation of the antibody with excess cognate peptide abolished all immunoreactivity. A threefold to sixfold increase in vascular endothelial growth factor messenger RNA expression occurs in secretory versus proliferative endometrial samples. Endometrial stromal and epithelial cell isolates from both phases of the menstrual cycle express VEGF121, VEGF165, and VEGF189 isoforms, however, vascular endothelial growth factor variant 206 was not detected. CONCLUSIONS: Expression of vascular endothelial growth factor in the endometrium throughout the menstrual cycle suggests that vascular endothelial growth factor may promote the vascular growth, maintenance, and hyperpermeability required for adequate receptivity in the cycling human endometrium.

Adult↗
PubMed1995

Abortion.

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Abortion, Induced↗
PubMed1995

Expression of cell cycle regulatory proteins (p53, pRb) in the human female genital tract.

PURPOSE: Recent studies have shown that proliferation and differentiation of various cell types is regulated by cell-cycle-related proteins, such as protein p53 and retinoblastoma protein pRb. METHODS: Three monoclonal antibodies to p53 (PAb240, PAb421, and PAb1801) and 3H9 monoclonal antibody to pRb were utilized for localization of proteins by peroxidase immunohistochemistry in frozen tissue sections. RESULTS: Nuclear and nucleolar p53 expression was detected in nondividing and relatively stable cells, e.g., oocytes in primordial follicles and granulosa lutein cells. On the other hand, strong cytoplasmic p53 expression was detected in proliferating and low differentiated epithelial cells of the ovarian surface epithelium, amnion, endocervix and ectocervix, indicating enhanced p53 synthesis. Not all three p53 antibodies reacted with each tissue, perhaps due to structural and conformational changes in the p53 molecule, accompanying p53 association with other proteins, e.g., tissue specific transcription factor interactions. pRb expression was usually restricted to the cell nuclei and nucleoli. However, glandular cells of the female reproductive tract showed cytoplasmic pRb expression in juxtaluminal (secretory) segments of cells, a feature not previously described in any cell type. p53 and pRb immunoreactivities declined with advanced differentiation of cells. No p53 or pRb was detected in placental syncytiotrophoblast or terminally differentiated squamous epithelial cells. CONCLUSION: Our data indicate that large quantities of p53 are synthesized in cells leaving the cell cycle and entering differentiation. Except in glandular cells, the pRb expression is confined to the cell nuclei and nucleoli. A unique cytoplasmic expression of pRb in juxtaluminal segments of glandular cells suggests a role for pRb in human female fertility and conception.

Antibodies, Monoclonal↗
PubMed1995

Quantitative evaluation of the cell cycle-related retinoblastoma protein and localization of Thy-1 differentiation protein and macrophages during follicular development and atresia, and in human corpora lutea.

Ovarian follicular development is dependent on growth and differentiation of the oocyte, as well as the granulosa and theca cell layers. The majority of primary follicles in the adult human ovary are not growing, and most antral follicles undergo atresia. The mechanisms regulating follicular growth and differentiation are poorly understood. Expression of key regulatory proteins in cells of certain follicles may be involved. We have studied the distribution of retinoblastoma protein (pRb), a key cell cycle regulator, in human follicles and CL by quantitative immunohistochemistry. Recent studies suggest that high nuclear concentrations of pRb are associated with the arrest of cell proliferation and the beginning of differentiation; during advanced differentiation of cells pRb is markedly depleted or absent. We also studied follicular distribution of Thy-1 differentiation protein, a morpho-regulatory molecule associated with cell differentiation, and the presence of macrophages. Macrophages have been shown to stimulate steroidogenesis in granulosa cells in vitro, and they are required for release of Thy-1 differentiation protein from vascular pericytes among granulosa cells in vivo. Our results indicate that oocytes in resting follicles exhibit pRb in the nucleoli. During initiation of follicular growth, the pRb expression first extends over the oocyte nuclei and then diminishes from both nuclei and nucleoli in preantral follicles. When the oocytes reach maximum size in small antral follicles, the pRb expression is reestablished in oocyte nucleoli. In differentiating granulosa and theca cell layers of preantral and small antral follicles, pRb expression is high, but it is low in growing large antral follicles. During CL development and regression, pRb expression in the nuclei of granulosa lutein cells first increases and then decreases. Follicular development is accompanied by the presence of Thy-1 differentiation protein and macrophages under the follicular basement membrane. In growing large antral follicles, during the mid-follicular phase, larger macrophages exhibit physical contacts with granulosa cells through the follicular basement membrane, and, during the late follicular phase, small dendritic macrophages can be detected among granulosa cells, but not within the follicular antrum. Large antral follicles undergoing atresia exhibit strong pRb expression in granulosa cells. This is accompanied by a lack of Thy-1 differentiation protein among granulosa cells and the occurrence of large phagocytic macrophages in the follicular antrum. This is the first report of pRb expression in the human ovary.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Cycle↗
PubMed1995

Is corpus luteum regression an immune-mediated event? Localization of immune system components and luteinizing hormone receptor in human corpora lutea.

Factors determining the life span of the human corpus luteum (CL) are not known. In addition to being determined by hormonal factors, such as hCG, the life of luteal cells may be determined by the preservation of luteal vascularization. Furthermore, the CL represents an immunologically unique tissue, as it is formed after menarche, long after adaptation of the immune system toward self. Thus, CL regression may be immunologically mediated. To determine what role the vasculature and immune system play in human CL development and regression, we examined immunohistochemically 1) the expression of Thy-1 differentiation protein by vascular pericytes, 2) the expression of major histocompatibility complex (MHC) class I and class II molecules in granulosa lutein cells (GLC), and 3) infiltration of the CL by macrophages and T lymphocytes. LH receptor (LHR) and cytokeratin 18 expression were also studied. In developing CL, the pericytes of luteal microvasculature released Thy-1 differentiation protein among the endothelial cells of proliferating vessels. In mature CL, Thy-1 released from vascular pericytes accumulated on the surface of GLC, and these cells exhibited LHR immunoreactivity (LHRI). Overall LHRI increased during the luteal phase and was strongest at the beginning of the late luteal phase. Although vascular pericytes showed strong LHRI, no staining of endothelium was detected during the luteal phase. GLC exhibited strong cytokeratin staining and moderate staining for MHC class I and MHC class II antigens; numerous macrophages were detected in luteal tissue. During pregnancy, the staining pattern was similar to that seen in the mature CL at the end of the midluteal phase. During the late luteal phase, surface expression of MHC class I and MHC class II antigens by GLC was substantially enhanced, and some T cells invaded among luteal cells. By the end of the cycle, an acute regression of vasculature and luteal tissue was observed along the fibrous septa. The remaining GLC showed only surface and no cytoplasmic LHRI. During the subsequent cycle, in the presence of numerous T cells, regressing GLC exhibited strong surface expression of various macrophage markers, such as CD4, CD14, CD68, and leukocyte common antigen, a feature not detected in the CL during the luteal phase nor described in other tissues. A complete loss of cytokeratin staining in GLC was observed. In regressing CL, strong LHRI was present in the endothelium of small and large luteal vessels. In conclusion, vascular pericytes and macrophages may stimulate the development and senescence of luteal tissue. The senescence of GLC may be inconsistent with preservation of luteal vasculature, and T lymphocytes appear to participate in terminal regression of the CL. Regression of luteal tissue therefore resembles immunologic rejection of a transplant. During pregnancy, the aging process of GLC appears to be interrupted, possibly due to the temporary acceptance of the CL "graft."

Adult↗
PubMed1995

Alcohol inhibits epidermal growth factor-stimulated progesterone secretion from human granulosa cells.

In this study, luteinized human granulosa cells (GC) obtained during in vitro fertilization procedures were used as a model system to evaluate the effects of ethanol (EtOH), a well-known reproductive toxin, on epidermal growth factor (EGF) and gonadotropin-stimulated steroidogenesis. Our results demonstrate that the basal progesterone (P4) and estradiol (E2) secretion by human GC in vitro was dependent on the ovarian stimulation protocol. EGF significantly enhanced P4, but not E2, secretion in human GC from clomiphene citrate (CC), human menopausal gonadotropin (hMG), and hMG/gonadotropin-releasing hormone agonist (GnRH-a)-treated patients. The effects of EGF plus luteinizing hormone (LH) were additive in cells from the CC group, but less than additive in hMG and hMG/GnRH-a groups. EtOH at 20 mM or more inhibited EGF stimulated P4 secretion in human GC from all three patient groups. EtOH inhibited P4 secretion stimulated by EGF and LH cotreatment in the CC and hMG/GnRH-a groups, but not in human GC from the hMG-treated patients. These results suggest that basal and EGF or LH-stimulated P4 secretion by human GC, as well as the effects of EtOH, are profoundly influenced by the follicle's hormonal milieu.

Cells, Cultured↗
PubMed1995

Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis.

PROBLEM: Formation of primordial follicles in adult ovaries could be a cryptic process limited to relatively small areas of the ovarian cortex and occurring during a certain stage of the menstrual cycle. Such an event may require a specific milieu provided by factors involved in developmental processes, i.e., morphoregulatory molecules and macrophages. METHOD: Adult human ovaries were investigated by immunohistochemistry for surface epithelium and granulosa cell markers (cytokeratin 18 and MHC class I), immune system-related morphoregulatory molecules (Thy-1 glycoprotein and N-CAM), and macrophage phenotypes (CD14, CD68, and MHC class II). RESULTS: In some ovaries 300-500 microns areas of surface epithelium were overgrown by tunica albuginea, descended into the stroma, and apparently fragmented into individual small (20-40 microns) follicle-like cell nests. Differentiation of the surface epithelium was accompanied by macrophages and Thy-1 glycoprotein. Small segments of surface epithelium showed N-CAM and a lacked MHC class I expression. In such segments, clear spherical germ-like cells migrated into the deeper stroma, associated with the microvasculature, and eventually aggregated with follicle-like cell nests. CONCLUSIONS: Our data suggest that surface epithelium may be involved in the formation of some primordial follicles in adult ovaries. This process, and further follicular fate, may require a precise interplay of immune system related morphoregulatory molecules and macrophages.

Adult↗
PubMed1995

IL-1 beta, TNF-alpha, and IL-2 in peritoneal fluid and macrophage-conditioned media of women with endometriosis.

PROBLEM: The presence of various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to the development of endometriosis, infertility, and activation of peritoneal macrophages. This study assesses levels of IL-1 beta, IL-2 and TNF- alpha in peritoneal fluid and macrophage conditioned media of women with endometriosis. METHOD: Peritoneal fluid was collected from 51 women at the time of diagnostic or operative laparoscopy for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IL-1 beta, IL-2, and TNF- alpha levels were determined by commercial ELISA kits. RESULTS: The mean concentration of IL-1 beta and TNF- alpha was significantly higher in macrophage conditioned media of patients with endometriosis (P < 0.02). However, there were no significant changes in peritoneal fluid cytokine levels. Peritoneal macrophage concentrations were also higher in patients with endometriosis. CONCLUSION: This study supports the concept that endometriosis is associated with activation of peritoneal macrophages, and a higher concentration of these cells. This activation is reflected by the increased levels of cytokines found in macrophage conditioned media. The absence of significant changes in peritoneal fluid cytokine levels would seen to indicate that the above derangements are not responsible for the development or progression of endometriosis.

Adult↗
PubMed1995

The steroidogenic and morphological effects of paclitaxel on cultured ovarian cancer cells.

We have studied the biochemical effects of paclitaxel (trade name Taxol) in three ovarian cancer (OV Ca) cell lines and JEG-3 choriocarcinoma cells. Paclitaxel (1 microgram/ml) was cytotoxic to approximately 80% of OV Ca cells, and the ED50 ranged from 6 to 9 ng/ml. Paclitaxel was also cytotoxic to JEG-3 cells (ED50 40 ng/ml), but even at 1 microgram/ml, 40-50% of the cells survived paclitaxel treatment. Paclitaxel increased 17 beta-estradiol secretion 3-4 fold in all three OV Ca cell lines with an ED50 range of 3-13 ng/ml. Similarly, paclitaxel increased estradiol secretion from JEG cells with an ED50 of 50 ng/ml. Colchicine also increased estradiol secretion significantly from OV Ca cells at 2 microM while reducing cell number approximately 40% (beta-lumicolchicine, an inactive isomer, was ineffective at this concentration). Paclitaxel (1 microgram/ml) treatment of BR OV Ca cells produced alterations in morphology leading to "rounding" of cells within 6 h of treatment. Simultaneously, paclitaxel increased immunohistochemical staining for aromatase, and this increase was coincident with morphological alterations. The present results demonstrate that low concentrations of paclitaxel can have significant steroidogenic, as well as cytotoxic, effects on OV Ca cells, suggesting that paclitaxel may activate signal transduction pathways in addition to disrupting microtubule function. These findings further suggest that paclitaxel could be efficacious at submicromolar concentrations.

Adenocarcinoma↗
PubMed1994

Ethanol modulates the hormone secretory responses induced by epidermal growth factor in choriocarcinoma cells.

Analysis of clinical data has implicated ethanol (EtOH) as an embryotoxic agent and as an agent that disrupts normal placental structure and function. Because epidermal growth factor (EGF) is an important regulator of placental function, we have studied the effects of EtOH on EGF-induced hormone secretion using JEG-3 choriocarcinoma cells that serve as a model for trophoblast cells. EtOH at physiological (5-100 mM) concentrations modulated effects of EGF in a time and dose-dependent manner. EGF-induced P4 secretion was increased by 20-100 mM EtOH after a 2-day pretreatment of cells with EtOH, but not after a 6-day pretreatment. Preincubation with 50 mM EtOH doubled the P4 responses to 50 and 100 ng/ml EGF. Although a 2- or 4-day preincubation of cells with 10-50 mM EtOH increased the secretion of E2 in response to 20 ng/ml EGF, a 6-day preincubation inhibited the secretory response to EGF. Pretreatment of cells with 10-50 mM, but not 100 mM EtOH for 2 to 6 days enhanced the human chorionic gonadotropin (hCG) secretory response to EGF. At 50 mm EtOH, the secretion of hCG in response to EGF was increased 2-fold. EtOH also increased basal hCG secretion in a dose-dependent manner between 10-50 mM EtOH. These results suggest that EtOH may modulate EGF-stimulated hormone secretion from cells of placental origin. Such alterations, if they occur in vivo, may impact on the function of the placenta and could potentially explain the pathophysiology of alcohol toxicity during pregnancy.

Cell Line↗
PubMed1994

Interferon-gamma (IFN-gamma) and interleukin-6 (IL-6) in peritoneal fluid and macrophage-conditioned media of women with endometriosis.

PROBLEM: The presence of the various cytokines in human peritoneal fluid has been incompletely evaluated. Changes in cytokine levels may be related to activation of peritoneal macrophages, development of endometriosis, and infertility. This study assesses peritoneal fluid levels of interferon gamma (IFN-gamma) and interleukin-6 (IL-6), and peritoneal macrophage production of IL-6, in women with and without endometriosis. METHOD: Peritoneal fluid was obtained from 62 women at the time of diagnostic or operative laparoscopic surgery for benign gynecologic disease. Peritoneal macrophages were isolated, cultured for 24 h, and the culture media collected. IFN-gamma and IL-6 levels in peritoneal fluid samples and macrophage conditioned media were determined by commercial ELISA. RESULTS: IL-6 was significantly higher in the macrophage conditioned media of women with endometriosis as compared with controls. IL-6 levels were fourfold higher in early stage endometriosis (P < 0.05) and eightfold higher in advanced endometriosis. There were no significant differences between groups in the peritoneal fluid levels of IL-6 or IFN-gamma. CONCLUSIONS: Peritoneal macrophage IL-6 secretion is increased in women with endometriosis, and appears to correlate with disease stage. IFN-gamma does not appear to be responsible for the activation of macrophages in women with endometriosis.

Adult↗
PubMed1994

The inhibitory action of taxol on granulosa cell steroidogenesis is reversible.

Taxol is a novel anticancer agent extracted from the bark of Pacific yew trees. The drug has been approved by the FDA for the treatment of advanced ovarian cancer and is in clinical trials for other malignancies, including breast cancer. The goals of this study were to determine whether taxol adversely and irreversibly affects ovarian granulosa cell steroidogenesis. Cultured porcine granulosa cells were treated with taxol (0.12-12 microM) or vehicle (0.01-1% ethanol) in the absence or presence of 10(-9) M hCG in a time- and dose-response study. Morphological changes were recorded every 2 h, and media were collected for the measurement of progesterone (P4) and 17 beta-estradiol. Taxol suppressed both basal P4 and 17 beta-estradiol production and hCG-stimulated P4 production in a time- and dose-dependent manner and drastically changed cell shape by causing disorganization of microtubule bundles and other subcellular organelles. hCG partially reversed the steroid inhibition induced by taxol. These changes are not attributed to ethanol used as the vehicle, because ethanol at higher concentrations than that present in taxol did not suppress P4 production. When taxol was removed from the culture, P4 production returned to control levels. The results of this study show that taxol causes a significant, but reversible, inhibition of granulosa cell steroidogenesis. This inhibitory effect can be partially overcome by co-treatment with hCG.

Animals↗
PubMed1993

Cellular localization of luteinizing hormone receptor immunoreactivity in the ovaries of immature, gonadotropin-primed and normal cycling rats.

In this study we used two monoclonal antibodies against purified LH receptor (LHR) to localize and quantify LHR in ovarian compartments during follicular development, using gonads from immature, gonadotropin-primed, and normal cycling rats. In early preantral follicles, LHR immunoreactivity (LHRI) was identified in vascular endothelium and subsequently appeared in vascular pericytes. In healthy small antral (200-550-microns) follicles, LHRI continued to be present in thecal pericytes, but not in cells of the theca interna. However, in small antral follicles undergoing atresia, a dramatic decrease in thecal vessel LHRI with a concomitant increase in LHRI in hypertrophied theca was observed. In healthy antral follicles, LHRI of thecal cells was not observed until the cells reached medium (550-microns) size. High LHRI was occasionally observed in macrophage-like cells adjacent to the oocyte of large preantral follicles and among granulosa layers of medium-sized antral follicles. In the membrana granulosa, LHRI first appeared in cumulus cells of medium-sized antral follicles and subsequently spread to the entire granulosa cell population of large (750 microns) antral follicles. Treatment of immature rats with eCG markedly enhanced LHRI in theca and granulosa cells of all antral follicles, while eCG/hCG-treated (pseudopregnant) rats showed lack of LHRI in follicles and interstitial glands, but not in corpora lutea (CL). Within degenerating CL in the cycling ovary, compared to fresh and mature CL, a significant decrease occurred in intracellular LHRI. Our observations indicate that 1) vascular pericytes may play a role in follicular development; 2) LHR expression in granulosa may require an interaction of macrophages, oocytes, and cumulus cells; and 3) thecal hypertrophy accompanied by enhanced LHR expression occurs on follicles undergoing atresia.

Aging↗
PubMed1993

Detection of fibrin D-dimer in plasma and urine of pregnant women using Dimertest latex assay.

Eighty-six women admitted for evaluation of preeclampsia had plasma and urine screened for the presence of fibrin D-dimer using the monoclonal antibody DD-3B6 in a latex fixation assay (Dimertest). In 53 of the women screened, results were negative for fibrin D-dimer in both plasma and urine; in 33, results were positive in urine (N = 11), plasma (N = 14), or both (N = 8). D-dimer positive women were at increased risk for earlier delivery (mean 34 versus 36 weeks), lower birth weight babies (mean 2,327 versus 2,669 g), higher mean arterial pressures (mean 104 versus 94mm Hg), liver function test abnormalities (mean lactate dehydrogenase value 256 versus 142 U/L, mean serum glutamic-oxaloacetic transaminase 67 versus 23 U/L), and significantly elevated levels (> 40 micrograms/mL) of fibrin(ogen) degradation products (FDPs). Interestingly, 22 of 33 D-dimer positive women had insignificant levels of FDPs. Generally, D-dimer negative women had no significant abnormalities in results of coagulation tests and liver function tests. This study confirms previous observations on the value of D-dimer detection in screening for preeclampsia coagulopathy and extends this tool to its detection in urine.

Adult↗
PubMed1992

The effect of peritoneal macrophage-derived factor(s) on ovarian progesterone secretion and LH receptors: the role of calcium.

Macrophages and their secretory products, cytokines, play an integral role in many reproductive processes. In this study we examined the effect of conditioned media from cultured human peritoneal macrophages on progesterone production by granulosa cells and the role of calcium in this process. Macrophages were pretreated with various concentrations of a calcium channel blocker (verapamil) or a calcium ionophore (A23187). Macrophage-conditioned media (MCM) or cell-free media that contained calcium channel modifiers were added at three dose levels to cultured porcine granulosa cells. Progesterone production and LH receptor content were determined. Macrophage-conditioned media alone elevated basal progesterone production, but significantly attenuated granulosa cell LH receptor content. These effects were neither potentiated nor suppressed by pretreating macrophages with verapamil. However, production of the LH receptor lowering factor(s) appeared to be suppressed by calcium ionophore. We conclude that (1) one or more factors produced by macrophages have a net stimulatory effect on basal progesterone production and these factor(s) may not be calcium-dependent and (2) macrophage-derived secretory products reduce granulosa cell LH receptor content. The production of these factor(s) may be calcium-dependent.

Animals↗
PubMed1991

Hypercalcemic crisis in pregnancy associated with excessive ingestion of calcium carbonate antacid (milk-alkali syndrome): successful treatment with hemodialysis.

Severe hypercalcemia, a potentially life-threatening condition, has been reported rarely during pregnancy. A patient with hypercalcemic crisis associated with excessive ingestion of absorbable calcium antacid was treated successfully with hemodialysis as well as other therapeutic measures, such as saline diuresis. This acute therapy resulted in long-term normalization of maternal calcium levels. The fetus, who exhibited a low biophysical score during the initial admission, was delivered a month later and had an uncomplicated neonatal course. Acute hemodialysis can be an effective, rapid, and safe method of lowering serum calcium levels in pregnant patients with severe hypercalcemia unresponsive to other medical therapies.

Adult↗