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Biomedical subjects

G Meduri

Publications and source records attributed to G Meduri.

At least 19 recordsLinked to original sources
PubMed2001

The expression of thyrotropin receptor in the brain.

The regulation of the thyroid gland by TSH is mediated by a heterotrimeric G protein-coupled receptor. Nonthyroid effects of TSH have been reported, and expression of its receptor has been described in adipocytes and lymphocytes. We have previously reported the existence of specific and saturable binding sites of TSH and specific TSH effects in primary cultured rat brain astroglial cells. We now report expression of the TSH receptor gene in these cells; the coding sequence of the corresponding complementary DNA is identical to that previously established in thyroid. Using specific antisense RNA probe, expression of this gene was detected in some isolated or clustered glial fibrillary acidic protein-positive primary cultured cells by in situ hybridization. With this technique, we further detected TSH receptor messenger RNA (mRNA) expression in rat brain cryoslices in both neuronal cells and astrocytes. Its presence predominated in neuron-rich areas (pyriform and postcingulate cortex, hippocampus, and hypothalamic nuclei) and was mostly colocalized with neuron-specific enolase. In astrocytes, this mRNA was detected in the ependymal cell layer and the subependymal zone, and several isolated cells were also found in the brain parenchyma. We also detected TSH receptor mRNA and protein in primary cultured human astrocytes. The protein was detected as well in both rat and human brain cryoslices. Together, these findings clearly demonstrate the expression of the TSH receptor gene in the brain in both neuronal cells and astrocytes.

Animals↗
PubMed2001

The postmenopausal ovary is not a major androgen-producing gland.

It is currently believed that the postmenopausal ovary remains a gonadotropin-driven, androgen-producing gland. However, the adrenal contribution to circulating androgen levels may explain some conflicting results previously reported. In addition, the steroidogenic potential and gonadotropin responsiveness of the postmenopausal ovary have not been recently reassessed. Plasma T, bioavailable T, free T, androstenedione (Adione), and dehydroepiandrosterone sulfate levels were measured in postmenopausal or ovariectomized women with complete adrenal insufficiency, compared with women with intact adrenals. A stimulation human chorionic gonadotropin test (on d 0, 3, and 6) was performed in postmenopausal women with adrenal insufficiency. Dexamethasone was administered for 4 d in postmenopausal women with intact adrenals. Intraovarian T and androstenedione were also measured in homogenates of ovarian tissue from postmenopausal women. Immunocytochemistry was performed on postmenopausal ovaries and premenopausal controls to detect the presence of steroidogenic enzymes (P-450 aromatase, P-450 SCC, 3beta HSD, and P-450 C17) and gonadotropin receptors. Plasma androgen levels were below or close to the limit of the assay in all women with adrenal insufficiency. They were similar in postmenopausal and oophorectomized women with normal adrenals. No hormonal changes were observed after human chorionic gonadotropin injections in women with adrenal insufficiency. In contrast, a dramatic decrease of all steroids was observed after dexamethasone administration in postmenopausal women with intact adrenals. Intraovarian T and androstenedione levels were negligible in postmenopausal ovarian tissue. P-450 aromatase was absent from the 17 ovaries studied, and the enzymes for androgen biosynthesis were either absent (n = 13) or present in very low amounts (n = 4). In all the postmenopausal ovaries, FSH and LH receptors were completely absent. In the absence of adrenal steroids, postmenopausal women have no circulating androgens. This result is consistent with the immunocytochemical studies showing the almost constantly absent steroidogenic enzymes and LH receptors in the postmenopausal ovary. Thus, the climacteric ovary is not a critical source of androgens. The arrest of androgen secretion after menopause may impact significantly on women's health.

Adrenal Glands↗
PubMed2001

Presence of estrogen receptor beta in the human endometrium through the cycle: expression in glandular, stromal, and vascular cells.

The recent discovery of a new isoform of estrogen receptor (ER) beta has prompted the reexamination of estrogen action on target organs. Here, we describe the endometrial expression of human ERbeta and compare its distribution with that of ERalpha in the endometrial functional zone. Using immunocytochemistry with well characterized polyclonal antibodies against ERbeta, we have detected specific ERbeta expression in all endometrial compartments (glandular, stromal, and vascular); the specificity of the immunostaining is confirmed by lack of staining of the uterine sections with anti-ERbeta antibodies previously incubated with peptide preparation. The highest levels of ERbeta expression are observed in epithelial cells during the periovulatory period (days 14 and 15), as well as in stromal cells and cells of the vascular wall in the late-secretory phase; both smooth muscle cells and endothelial cells express ERbeta, as deduced from immunocytochemistry and RT-PCR analysis. ERbeta staining is usually low compared with that of ERalpha, except at days 24-26. The presence of ERbeta in decidualized stromal cells is deduced from immunocytochemistry using antismooth alpha-actin and anti-ERbeta antibodies or from RT-PCR analysis of ERbeta and insulin-like growth factor-BP transcripts in the same cells; the presence of ERbeta-positive stromal cells located close to vascular smooth muscle cells during this period suggests some specific role of this receptor during decidualization. ERalpha is also present in the cells of the endometrial vascular wall, in addition to the nuclei of glandular epithelial and stromal cells. Vascular ERalpha expression is highest during the periovulatory period, suggesting a regulation by estradiol, and a role in vascular function. Moreover, different variations of ERbeta and ERalpha in arterioles might have implications for the modulation of vascular function, possibly of vascular tone, during the menstrual cycle. Finally, these data suggest that ERbeta may have important roles in endometrial function, in addition to the well known role of ERalpha in endometrial proliferation and differentiation.

Adult↗
PubMed2000

Vasopressin V1a receptor signaling in a rat choroid plexus cell line.

A new cell line was derived from primary culture of rat choroid plexus (RCP) by immortalization with the TSOri minus adenovirus. The selected clone expressed vasopressin V1a receptors at a density of 64,000 sites per cell, and a K(d) of 7.2 nM. Addition of vasopressin to the RCP cells induced a transient calcium peak comparable to V1a receptor signalling in different expression systems. This [Ca(2+)](i) increase was dose-dependent with an EC(50) of 22 nM vasopressin. Similar [Ca(2+)](i) increase was elicited by addition of serotonin, angiotensin II, endothelin-1, and bradykinin. Heterologous desensitization of V1a receptor was observed in RCP cells exposed to the phorbol ester PMA or following stimulation of other receptors coupled to the phosphoinositide pathway. Positive immunolabelling with Factor VIII, Flt1 and CD 34 antibodies suggests that this new RCP cell line originated from endothelial cells of rat choroid plexus.

Animals↗
PubMed2000

Expression of vascular endothelial growth factor receptors in the human endometrium: modulation during the menstrual cycle.

Angiogenesis is fundamental for human endometrial development and differentiation necessary for implantation. These vascular changes are thought to be mediated by the vascular endothelial growth factor (VEGF), whose specific receptors have not been examined in detail thus far. We conducted the present study to determine, by immunocytochemistry and computerized image analysis of the functionalis, the expression and modulation of the receptors Flk-1/KDR and Flt-1, which mediate VEGF effects on endothelial mitogenicity, chemotaxis, and capillary permeability. VEGF receptors are expressed mainly in endometrial endothelial cells, with variations of intensity and number of stained capillaries related to the phase of the cycle. The number of capillaries immunostained for Flk-1/KDR was maximal in the proliferative phase (ratio Flk-1/CD34: 1), twice as high as the number of Flt-1-expressing capillaries (ratio Flt-1/CD34: 0.47). The staining intensity for Flk-1 decreased during the late proliferative and early secretory phases, to increase again in the midsecretory period. The number of Flt-1-labeled capillaries was about 2-fold higher in the secretory than in the proliferative phase; however, the proportion of Flt-1-positive cells did not change, owing to the associated increase in vascular density that characterizes progression of the functionalis from the proliferative to the secretory stage. The staining intensity for Flt-1 was higher during the late proliferative and secretory phases (especially in the midsecretory phase) and the premenstrual period. In contrast, the proportion of capillaries expressing Flk-1/KDR decreased in the secretory phase (ratio Flk-1/Von Willebrand factor: 0.55). Enhanced expression of Flk-1/KDR, and of Flt-1, on narrow capillary strands at the beginning of and during the proliferative phase may account for the rapid capillary growth associated with endometrial regeneration following menstrual shedding. The high coexpression of Flk-1/KDR and Flt-1 observed on capillaries during the midsecretory period correlates with an increase of endometrial microvascular density and of permeability characteristic of this phase of the cycle, which is a prerequisite for implantation. Finally, strong expression of Flt-1, but not Flk-1/KDR, was observed on dilated capillaries during the premenstrual period and the late proliferative phase, suggesting preferential association of Flt-1 with nonproliferating capillaries at those times; activation of this receptor by VEGF could be involved in premenstrual vascular hyperpermeability, edema, and extravasation of leukocytes. In addition to the endothelial localization, we found that epithelial cells expressed Flt-1 and Flk-1/KDR. We conclude that Flt-1 and Flk-1/KDR in the functionalis are modulated in parallel or independently according to the phase of the cycle, and that these changes are responsible for VEGF actions on endometrial vascular growth and permeability. The molecular mechanisms concerning these regulations will require further investigation.

Adult↗
PubMed2000

Gastric permeability to sucrose is increased in portal hypertensive gastropathy.

BACKGROUND: Portal hypertensive gastropathy (PHG) is frequently found among patients with hepatic cirrhosis and at present the only way to detect and follow PHG is via endoscopy. OBJECTIVE: To assess gastric and intestinal permeability and investigate its relationship to endoscopic findings and indices of portal hypertension and hepatic function. DESIGN AND METHODS: Thirty-one non-diabetic patients with hepatic cirrhosis and PHG (PHG+) were studied and compared with 17 cirrhotic patients without PHG (PHG-). All patients underwent endoscopy for the assessment of PHG and Helicobacter pylori status, ultrasound determination of the diameters of spleen and portal vein, and, subsequently, an oral load of sucrose, lactulose, and mannitol. Sugar concentrations were determined in 6-h urine specimens and expressed as a percentage of the orally administered dose or as lactulose/mannitol ratio. RESULTS: The urinary sucrose excretion was significantly elevated in patients with PHG compared to those without (PHG+, 0.20% +/- 0.03; PHG-, 0.07% +/- 0.01; P< 0.001). No difference was found for the small intestinal probes lactulose and mannitol. Gastric sucrose permeability correlated positively with the endoscopic lesion score (P < 0.001), but not with other parameters of portal hypertension or hepatic function. H. pylori status did not influence gastric permeability. The sensitivity of this test reached 100% for PHG scores > 2. CONCLUSIONS: Gastric permeability to sucrose is increased in patients with PHG, independently of the presence of H. pylori. Sucrose permeability may be useful for the follow-up of patients with PHG.

Female↗
PubMed2000

Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary.

TSH secretion from the anterior pituitary is mainly regulated by TRH and thyroid hormones. We hypothesized that in addition the pituitary itself could modulate TSH production by sensing its own TSH release, enabling fine-tuning of TSH secretion. For such an ultra-short loop control, the pituitary should contain a TSH receptor (TSH-R). To find evidence for this we screened a human pituitary complementary DNA library with a digoxigenin-labeled TSH-R probe and found 2 positive clones of 32,000 plaques. One clone was sequenced and found to be completely identical to the thyroid TSH-R. Further proof was obtained by RT-PCR on a human anterior pituitary obtained at autopsy. In situ hybridization and immunohistochemistry confirmed the presence of TSH-R in the anterior pituitary at the messenger ribonucleic acid level as well as the protein level. Moreover, double labeling experiments revealed that TSH-R messenger ribonucleic acid as well as TSH-R protein colocalize with major histocompatibility complex class II expression of folliculo-stellate cells. We conclude that TSH-R is expressed in a subpopulation of folliculo-stellate cells in the human anterior pituitary. This finding suggests ultra-short loop regulation of TSH secretion. Putative recognition of the pituitary TSH-R by TSH-R antibodies might have clinical relevance in Graves' disease.

Adult↗
PubMed2000

Relationship between myocardial 123I-metaiodobenzylguanidine scintigraphic uptake and heart rate variability in patients with syndrome X.

BACKGROUND: We have recently demonstrated a striking impairment in cardiac uptake of 123I-metaiodobenzylguanidine (MIBG) in most patients with syndrome X. In this study we investigated the relationship between cardiac MIBG defects and cardiac autonomic activity in these patients. METHODS: MIBG myocardial scintigraphy and time-domain and frequency-domain heart rate variability (HRV) were compared in 11 syndrome X patients and 10 healthy controls. Cardiac MIBG uptake was assessed by the heart/mediastinum ratio and a cardiac MIBG uptake defect score (higher values = lower uptake). RESULTS: The heart/mediastinum ratio was lower (1.71 +/- 0.6 vs 2.19 +/- 0.3, p = 0.03) and MIBG uptake score higher (37.1 +/- 32 vs 4.0 +/- 2.5, p = 0.005) in syndrome X patients, whereas average HRV values did not differ between the two groups. However, while there were no correlations between MIBG uptake and HRV in controls, in syndrome X patients both the heart/mediastinum ratio and MIBG uptake score correlated significantly with two HRV parameters, specific for vagal activity: the square root of the mean squared differences of consecutive RR intervals (r = 0.73, p = 0.01, and r = -0.67, p = 0.02, respectively), and high frequency (r = 0.64, p = 0.03, and r = -0.74, p = 0.009, respectively). CONCLUSIONS; In patients with syndrome X, the impairment in cardiac MIBG uptake was associated with a reduction in HRV indexes mainly reflecting vagal modulation of sinus node, thus suggesting that a predominance of cardiac adrenergic activity may be present in those with abnormal cardiac MIBG scintigraphy.

3-Iodobenzylguanidine↗
PubMed1999

Quantitative comparison of technetium-99m tetrofosmin and thallium-201 images of the thyroid and abnormal parathyroid glands.

The aim of the study was to quantitatively compare the scintigraphic images of the thyroid and abnormal parathyroid glands obtained with technetium-99m tetrofosmin and thallium-201 in patients with hyperparathyroidism. Forty-six patients with hyperparathyroidism underwent (201)Tl (74 MBq), (99m)Tc-pertechnetate (74 MBq) and (99m)Tc-tetrofosmin (555-740 MBq) scintigraphy in a single session. Image analysis included the computation of the thyroid/background ratio in the whole study population and the parathyroid/background ratio, parathyroid/thyroid ratio and diagnostic sensitivity in 17 patients who underwent parathyroid surgery. The pertechnetate subtraction technique was used. (201)Tl and (99m)Tc-tetrofosmin showed a similar thyroid/background ratio (1.79+/-0.41 and 1.81+/-0. 47, respectively, P=NS); however, (99m)Tc-tetrofosmin showed a higher parathyroid/background ratio than (201)Tl (2.06+/-0.54 vs 1. 79+/- 0.50, P=0.007). Despite the superior quality of (99m)Tc-tetrofosmin images, both tracers showed identical sensitivity in detecting enlarged parathyroid glands in patients with primary hyperparathyroidism (89%) and in those with secondary hyperparathyroidism (50%).

Adenoma↗
PubMed1999

Expression of metalloproteinases and their inhibitors in blood vessels in human endometrium.

Matrix metalloproteinases (MMPs) are zinc-requiring enzymes that can degrade components of the extracellular matrix and that are implicated in tissue remodeling. Their role in the onset of menstruation in vivo has been proven; however, the expression and functions of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in vascular structures are poorly understood. We determined by immunocytochemistry, using characterized monoclonal antibodies, the distribution of MMPs and of their inhibitors TIMP-1 and TIMP-2 in the endometrium during the menstrual cycle. MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 had differing distributions and patterns of expression. In addition to the localization of MMP-9 in the epithelium and of MMP-2, MMP-3, and MMP-1 in the stromal tissue, these MMPs were detected in the vascular structures. MMP-2 (72-kDa gelatinase) and tissue inhibitors TIMP-1 and TIMP-2 were detectable in vessels throughout the cycle. In contrast, MMP-3 (stromelysin-1) was detected only in late-secretory and menstrual endometrial vessels, while MMP-9 (92-kDa gelatinase) was detected in spiral arteries during the secretory phase and in vascular structures during the midfollicular and menstrual phases. The expression of MMP-2 and MMP-9 in endometrial vessels during the proliferative and secretory periods suggests their relationship to vascular growth and angiogenesis. The pronounced expression of MMP-3 (stromelysin-1) in the vessels situated in the superficial endometrial layer during menses suggests that this metalloproteinase initiates damage in the vascular wall during menstrual breakdown. The finding of an intense expression of TIMP-1 and TIMP-2 in the vessels delineating necrotic from non-necrotic areas during menses also suggests that they could limit tissue damage, allowing regeneration of the endometrium after menses. These data indicate that, in addition to expression in epithelial cells and stromal tissue, MMPs are expressed in endometrial vascular cells in a cycle-specific pattern, consistent with regulation by steroid hormones and with specific roles in the vascular remodeling processes occurring in the endometrium during the cycle.

Adult↗
PubMed1999

The antigonadotropic activity of a 19-nor-progesterone derivative is exerted both at the hypothalamic and pituitary levels in women.

We have previously shown in postmenopausal women that a 19-nor-progesterone derivative, nomegestrol acetate (NOMA) had a strong antigonadotropic activity and that this effect was not mediated via the androgen receptor. The aim of the present study was to further assess the action of this progestin on gonadotropin secretion in women. To demonstrate at which level of the hypothalamo-pituitary-ovarian axis the gonadotropin inhibition was exerted, 10 normally cycling (NC) women, 3 women with a gonadotropin-independent ovarian function [McCune-Albright (MCA) syndrome], and 5 women with functional hypothalamic amenorrhea (FHA) participated in the study. NC women were treated orally with 5 mg NOMA for 21 days, after one control cycle. Plasma estradiol (E2) and progesterone, LH, and FSH levels were measured during each cycle. A frequent sampling study (every 10 min for 4 h), followed by a classic GnRH test (100 microg, i.v.), was performed on day 11. Women with MCA were studied before, during NOMA, and after long-acting GnRH agonist administration. In women with FHA, pulsatile GnRH (20 microg s.c., every 90 min) was given for two cycles with or without NOMA (5 mg for 21 days). In all NC women, ovulation was suppressed by NOMA. Mean plasma LH levels, LH pulse frequency, and the LH response to exogenous GnRH were significantly decreased. In MCA, neither NOMA nor GnRH agonist modified multiple ovarian cysts on ultrasound or plasma E2, levels which remained elevated, ruling out a direct ovarian effect. In FHA, pulsatile GnRH administration recreated a normal ovulatory menstrual cycle. Addition of NOMA prevented the increase of plasma E2, decreased the amplitude of LH pulses, and prevented ovulation. In view of this unexpected action of NOMA at the pituitary level, seven samples of normal human female pituitaries were tested for the presence of progesterone receptor (PR) using a double labeling immunocytochemical technique. The presence of PR was detected in the seven human pituitary tissues. In addition, PR was found to be expressed only in gonadotroph cells. In conclusion, NOMA, a 19-nor-P derivative, has a potent antigonadotropic activity exerted at the hypothalamic level, inhibiting ovulation in NC women. In women with FHA, NOMA decreased the gonadotropin stimulation induced by pulsatile GnRH administration. According to the presence of PR in gonadotroph cells of normal human pituitaries, 19-nor-progesterone derivatives may also act on the gonadotropin secretion at the pituitary level.

Adolescent↗
PubMed1999

New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype.

Premature ovarian failure occurs in almost 1% of women under age 40. Molecular alterations of the FSH receptor (FSHR) have recently been described. A first homozygous mutation of the FSHR was identified in Finland. More recently, we described two new mutations of the FSHR in a woman presenting a partial FSH-resistance syndrome (patient 1). We now report new molecular alterations of the FSHR in another woman (patient 2) who presented at the age of 19 with primary amenorrhea contrasting with normal pubertal development. She had high plasma FSH, and numerous ovarian follicles up to 3 mm in size were evidenced by ultrasonography. Histological and immunohistochemical examination of ovarian biopsies revealed the presence of a normal follicular development up to the antral stage and disruption at further stages. DNA sequencing showed two heterozygous mutations: Asp224Val in the extracellular domain and Leu601Val in the third extracellular loop of FSHR. Cells transfected with expression vectors encoding the wild type or the mutated Leu601Val receptors bound hormone with similar affinity, whereas binding was barely detectable with the Asp224Val mutant. Confocal microscopy showed the latter to have an impaired targeting to the cell membrane. This was confirmed by its accumulation as a mannose-rich precursor. Adenylate cyclase stimulation by FSH of the Leu601Val mutant receptor showed a 12+/-3% residual activity, whereas in patient 1 a 24+/-4% residual activity was detected for the Arg573Cys mutant receptor. These results are in keeping with the fact that estradiol and inhibin B levels were higher in patient 1 and that stimulation with recombinant FSH did not increase follicular size, estradiol, or inhibin B levels in patient 2 in contrast to what was observed for patient 1. Thus, differences in the residual activity of mutated FSHR led to differences in the clinical, biological, and histological phenotypes of the patient.

Adenylyl Cyclases↗
PubMed1998

A novel phenotype related to partial loss of function mutations of the follicle stimulating hormone receptor.

A single natural loss of function mutation of the follicle stimulating hormone receptor (FSHR) has been described to date. Present in the Finnish population it markedly impairs receptor function, blocking follicle development at the primary stage and presenting as primary amenorrhea with atrophic ovaries. When Western European women with this phenotype were examined for FSHR mutations the result was negative, suggesting that other etiologies corresponding to this clinical pattern are markedly more frequent. We now describe a novel phenotype related to mutations provoking a partial loss of function of the FSHR. A woman with secondary amenorrhea had very high plasma gonadotropin concentrations (especially FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at ultrasonography. Histological and immunohistochemical examination of the ovaries showed normal follicular development up to the small antral stage and a disruption at further stages. The patient was found to carry compound heterozygotic mutations of the FSHR gene: Ile160Thr and Arg573Cys substitutions located, respectively, in the extracellular domain and in the third intracellular loop of the receptor. The mutated receptors, when expressed in COS-7 cells, showed partial functional impairment, consistent with the clinical and histological observations: the first mutation impaired cell surface expression and the second altered signal transduction of the receptor. This observation suggests that a limited FSH effect is sufficient to promote follicular growth up to the small antral stage. Further development necessitates strong FSH stimulation. The contrast between very high FSH levels and normal sized ovaries with antral follicles may thus be characteristic of such patients.

Adult↗
PubMed1998

Gonadotropin receptors and the control of gonadal steroidogenesis: physiology and pathology.

Over the past few years, knowledge of the structure of gonadotropin receptors and their mode of action has rapidly advanced. The cDNA corresponding to the luteinizeng hormone (LH) receptor (LHR) has been cloned, leading to the identification of a novel family of G-protein-coupled receptors. The follicle stimulating hormone (FSH) receptor (FSHR) was thereafter cloned by cross-hybridization with the LHR. Structure-function relationships have been studied by mutagenesis experiments in several laboratories. The cloning and chromosomal localization to chromosome 2p21 of the two human gonadotropin receptor genes has provided insights into their evolutionary relationships. The LHR and FSHR genes are very large and contain 10 and 11 exons respectively. The obtention of monoclonal antibodies against the receptors resulted in the characterization of the receptor proteins. These antibodies also allowed the study of receptor expression in target cells in physiological and pathological conditions. The internalization of the LHR has been studied by electron microscopy. A mechanism of receptor-mediated transcytosis through the endothelial cells of the testes has been described for the LHR. The polarized expression of receptors has been studied. The cloning of gonadotropin receptor genes has opened the field of genetic study of the receptors. Inactivating mutations of the LHR have been described in Leydig cell agenesis or hypoplasia. Different phenotypes, including complete pseudohermaphroditism, ambiguous genitalia and male phenotype, have been described. In the case of the FSHR, only one mutation has been reported in familial ovarian dysgenesis with primary amenorrhea. Related males have variable alterations of spermatogenesis and fertility. Constitutive mutations of the LHR have been reported in familial testotoxicosis. One similar mutation has also been described for the FSHR. Such mutations may lead to the development of a model of receptor activation.

Female↗
PubMed1998

Luteinization and proteolysis in ovarian follicles of Meishan and Large White gilts during the preovulatory period.

This experiment was conducted to determine why follicles luteinize faster in the Meishan breed than in the Large White breed of pig. Follicles were recovered during the late follicular phase from ovaries of both breeds before and after administration of hCG given to mimic the LH surge. First, the patterns of cholesterol transporters (high and low density lipoproteins: HDL and LDL) were compared. Cholesterol transporters detected in follicular fluid consisted of HDL only. Similar amounts of Apolipoprotein A-I were found in all samples. There was no obvious breed effect on minor lipoproteins found in the HDL-rich fraction, and this pattern was altered similarly by hCG in the two breeds. The LDL-rich samples of serum from both breeds contained similar amounts of protein. Second, three steroidogenic enzymes, adrenodoxin, 17 alpha-hydroxylase-lyase (P450(17) alpha) and 3 beta-hydroxysteroid-dehydrogenase (3 beta-HSD) were detected by immunohistochemistry and quantified by image analysis on sections of the two largest follicles. Before hCG treatment, theca interna cells demonstrated immunoreactivities for adrenodoxin (strong), P450(17) alpha and 3 beta-HSD (very strong), whereas granulosa cells displayed immunoreactivities for adrenodoxin only. After hCG treatment, the localization of the enzymes was unchanged but the staining intensity of adrenodoxin on granulosa cells and 3 beta-HSD on theca cells increased (P < 0.01 and P < 0.05, respectively). Breed effects were detected for the amounts of adrenodoxin in theca cells (Meishan > Large White; P < 0.05) and of 17 alpha-hydroxylase (Large White > Meishan, P < 0.01). Breed x treatment interactions were never detected. Finally, gelatinases, plasminogen activator, plasminogen activator inhibitor, tissue inhibitors of metalloproteases (TIMP-1 and TIMP-2) were visualized by direct or reverse zymography or western blotting. Whatever the stage relative to LH administration, follicular fluid from Large White gilts contained more TIMP-1, and TIMP-2 (P < 0.02 and P < 0.01, respectively). No breed effect was detected for the amounts of gelatinases and plasminogen activator inhibitor 1. However, for these parameters, a significant breed x time interaction was obvious, as the Meishan follicles had a greater response to hCG (P < 0.01). Since proteolysis plays a key role in the bioavailability of growth factors such as insulin-like growth factor 1, fibroblast growth factor and transforming growth factor beta, which have the ability to alter gonadotrophin-induced progesterone production in pigs, the differences observed in its control in the present study may explain, at least in part, the different patterns of luteinization observed in Meishan and Large White follicles.

3-Hydroxysteroid Dehydrogenases↗
PubMed1997

Abnormal cardiac adrenergic nerve function in patients with syndrome X detected by [123I]metaiodobenzylguanidine myocardial scintigraphy.

BACKGROUND: Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries). METHODS AND RESULTS: To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study. CONCLUSIONS: In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.

3-Iodobenzylguanidine↗
PubMed1997

Luteinizing hormone/human chorionic gonadotropin receptors in breast cancer.

Recent studies have suggested that human choriogonadotropin (hCG), in addition to its function in regulating steroidogenesis, may also play a role as a growth factor. Immunocytochemistry using two different monoclonal antibodies (LHR29 and LHR1055) raised against the human luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor allowed us to detect this receptor in breast cancer cell lines (T47D, MCF7, and ZR75) in individual cancer biopsies and in benign breast lesions. The receptor was also present in epithelial cells of normal human and sow breast. In the latter, its concentration increased after ovulation. The presence of LH/hCG receptor mRNA was confirmed by reverse transcription-PCR using primers extending over exons 2-4, 5-11, and 9-11. The proportion of LH/hCG-receptor positive cells and the intensity of the immunolabeling varied in individual biopsies, but there was no obvious correlation with the histological type of the cancer. These results are compatible with previous studies suggesting that during pregnancy, hCG is involved in the differentiation of breast glandular epithelium and that this hormone may play an inhibitory role in mammary carcinogenesis and in the growth of breast tumors.

Adult↗