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Biomedical subjects

H Meunier

Publications and source records attributed to H Meunier.

At least 19 recordsLinked to original sources

Simulation code for the interaction of 14 MeV neutrons on cells.

The structure of the survival curve of melanoma cells irradiated by 14 MeV neutrons displays unusual features at very low dose rate where a marked increase in cell killings at 0.05 Gy is followed by a plateau for survival from 0.1 to 0.32 Gy. In parallel a simulation code was constructed for the interaction of 14 MeV neutrons with cellular cultures. The code describes the interaction of the neutrons with the atomic nuclei of the cellular medium and of the external medium (flask culture and culture medium), and is used to compute the deposited energy into the cell volume. It was found that the large energy transfer events associated with heavy charged recoils can occur and that a large part of the energy deposition events are due to recoil protons emitted from the external medium. It is suggested that such events could partially explain the experimental results.

Cell Survival↗

Hybridization histochemical and immunohistochemical localization of inhibin/activin subunits and messenger ribonucleic acids in the rat brain.

Inhibin and activin are best known as gonadal glycoprotein hormones but have a broad anatomical distribution. We previously described the central distribution ofinhibin/activin beta A- and beta B-subunit proteins in some neuronal cell bodies, fibers, and nuclei of the rat brain and reported a possible role for central activin in suckling-induced oxytocin secretion and corticotropin releasing factor release. In the present report, we mapped the detailed immunohistochemical localization of inhibin/activin alpha-, beta A-, and beta B-subunits throughout the rat brain to further clarify their central distribution. In addition, the localization and distribution of their corresponding mRNAs was assessed. The results are summarized as follows: 1) Both beta A- and beta B-subunit immunoreactivity are found in neuronal cell bodies in the nucleus of the solitary tract and the dorsal and ventral medullary reticular nuclei, and in fibers and terminals of known projection sites for these nuclei. 2) beta B-subunit immunoreactivity is localized in a group of perifornical neurons in the hypothalamus. 3) beta A-subunit immunoreactivity is present in discrete populations of neuronal cell nuclei scattered throughout the CNS. 4) mRNAs encoding each of the inhibin/activin subunits are expressed in all major brain regions as determined by S1 nuclease assay and in a variety of specific neuroanatomical sites as shown by in situ hybridization. The results suggest that central inhibin and activin proteins are produced in the brain where they may potentially serve inter- and intracellular functions in multiple systems.

Activins↗

CFTR expression is regulated during both the cycle of the seminiferous epithelium and the oestrous cycle of rodents.

Severely reduced fertility is a common finding in cystic fibrosis (CF). We used in situ hybridization to examine the cell-specific expression of CFTR in the reproductive organs of rodents. In males CFTR mRNA is found in the round spermatids (spermatogenic stages V-X) and in the principal cells that line the initial segment of the epididymis. In both the testis and the epididymis, CFTR expression is developmentally regulated suggesting that the defect in the genital tract of male CF patients is of developmental origin. CFTR expression in the luminal and glandular epithelium of the uterus is regulated during the oestrous cycle and is maximal at pro-oestrus. Our results provide a biological rationale for the reduced fertility of CF patients, and suggest a possible cause for the comparatively poorer prognosis for women with CF.

Animals↗

Inhibin subunits in human placenta: localization and messenger ribonucleic acid levels during pregnancy.

This study describes the difference in distribution and levels of inhibin alpha, beta A- and beta B-subunit messenger ribonucleic acids in human placenta during pregnancy. Northern blot analysis indicated that inhibin alpha messenger ribonucleic acid is present in placental extracts collected at the early stage of gestation. Hybridization to inhibin beta A messenger ribonucleic acid was detected in the first trimester but in much lower levels. However, the intensity of the hybridization signal for inhibin alpha- and beta A-subunit messenger ribonucleic acids was greater in extracts prepared from term placentas than in those from the first or second trimester of pregnancy. Low levels of inhibin beta B-subunit messenger ribonucleic acid were observed only in extracts prepared from term placenta. At both early stage and term gestation trophoblast cells showed a positive fluorescent signal with the inhibin alpha-, beta A- and beta B-subunit-specific antisera. However, whereas inhibin alpha-subunit was localized in the cytotrophoblast, inhibin beta B-subunit immunoreactivity was observed in the syncytial layer of the villi, and inhibin beta A-subunit was widely distributed. The different distribution of immunoreactive inhibin subunits was confirmed by in situ hybridization, showing the different localizations of the inhibin messenger ribonucleic acids. These results showed that (1) human placenta produces the inhibin alpha- and beta A-subunits as early as the first trimester of pregnancy, (2) messenger ribonucleic acid levels for each of the three inhibin subunits are highest at term, and (3) immunoreactive inhibin subunits are localized differently in placental villi.

Female↗

Hypercalcaemia in acute adrenal insufficiency. A case report.

A woman aged 62 developed a septic shock and pulmonary embolism after skin grafting for extensive burns. She was put on anticoagulants. A second shock led to renal insufficiency. Hypercalcaemia developed. A CT scan of the upper abdomen disclosed enlarged adrenal glands. An acute adrenal haemorrhage was suspected. The levels of cortisol were low in the plasma and urine and did not respond to ACTH stimulation. Cortisone replacement therapy improved the condition of the patient and normalized plasma calcium levels. The mechanisms of hypercalcaemia in acute adrenal insufficiency are discussed. Multiple factors have been proposed: haemoconcentration, an increased affinity of plasma proteins for calcium, an increase in the filtrable calcium complexes, and an enhanced calcium mobilization of skeletal origin.

Acute Disease↗

Presence and synthesis of inhibin subunits in human decidua.

A growing number of studies provided the evidence that human decidua is a pregnancy-related tissue capable of hormone production and metabolism. The aim of the present study was to evaluate the possible presence of inhibin subunits in human decidua. Tissue samples were collected in pregnant women during the first (8 weeks) and second trimester (18 weeks) of gestation and at term (40 weeks). Immunohistochemical data were obtained using affinity purified polyclonal antisera raised in rabbit against porcine alpha, beta A, or beta B subunits. Levels of the respective inhibin subunits were evaluated by Northern blot analysis using cDNA probes encoding sequences corresponding to each subunit. The present results indicated that human decidua contains and synthesizes inhibin alpha, beta A, and beta B subunits. The immunohistochemical data showed that decidual cells were stained with both inhibin alpha and beta B antisera, showing a similar localization. On the other hand, cells stained with inhibin beta A antisera were sparse and followed a distribution pattern different from that of cells stained with alpha or beta B antisera. The first inhibin alpha and beta B subunit mRNAs were both expressed in first trimester of pregnancy, and those mRNA levels showed a gestational related increase. The beta A subunit mRNA was expressed at very low levels at term and could not be detected earlier during pregnancy. The present data showed that human decidua actively produces inhibin subunits with a gestational-related profile. The results suggest that decidua may be a further source of inhibin-related proteins during pregnancy and emphasize the endocrine competence of human decidua.

Abortion, Spontaneous↗

Primary sclerosing cholangitis and idiopathic pulmonary fibrosis: a case report.

Primary sclerosing cholangitis (PSC) and idiopathic pulmonary fibrosis (IPF) were each separately described in association with a variety of chronic idiopathic inflammatory diseases such as retroperitoneal fibrosis, Sicca complex or Riedel's thyroiditis. We report a case which may be the first description of the association between PSC and IPF. The physiopathogenic implications of such an association are discussed.

Biopsy↗

Possible involvement of inhibin in altered follicle-stimulating hormone (FSH) secretion during dissociated luteinizing hormone (LH) and FSH release: unilateral castration and experimental cryptorchidism.

Male rats were either unilaterally or bilaterally castrated, or were rendered cryptorchid when they were either 15 or 45 days old. Subsequently, blood was sampled over the next several weeks and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and immunoreactive inhibin-alpha (irI alpha) levels were measured by specific radioimmunoassays (RIAs). At the end of the experiment, gonadal expression of inhibin-alpha, inhibin-beta A, and inhibin-beta B subunits was measured by S1 nuclease analysis and in situ hybridization. In both age groups, bilateral castration (BC) produced the expected marked (p less than or equal to 0.01) increases in plasma LH and FSH levels, and concomitant decreases in T and irI alpha secretion within 1 - 2 days after surgery. In 15-day-old animals, unilateral castration (UC) significantly increased FSH and decreased circulating levels of irI alpha, but did not measurably alter LH or androgen production. At 7 days after surgery, the level of inhibin mRNA in the remaining testis was unchanged. In 45-day-old animals, UC caused a measurable increase in FSH, with little or no changes in the circulating levels of irI alpha. Plasma T levels were lowered (p less than or equal to 0.05) by UC; however, there were no statistical changes in LH levels in these UC rats. Finally, T administration markedly reversed UC-induced increase in FSH secretion in both age groups. Androgen therapy also interfered with inhibin release in 45-day-old, but not in 15-day-old rats. In rats 15 days old at the time of surgery, cryptorchidism produced a small but measurable increase (p less than or equal to 0.05) in LH release at Week 6 only, which was accompanied by a significant (p less than or equal to 0.01) decline in T secretion. Plasma FSH levels were elevated at all times in cryptorchid rats, and at 2, 4, and 6 wk, these levels were not statistically distinguishable (p greater than 0.05) from those of castrated animals. In this group of rats, cryptorchidism caused a transient increase (p less than or equal to 0.05) in irI alpha values 1 wk after surgery, but no changes at later times. Finally, measurement of testicular inhibin-alpha subunit messenger RNA (mRNA) levels showed an approximately 2-fold increase compared to total RNA levels in the testis. However, because of the significant decrease in total RNA levels per testis caused by cryptorchidism, the absolute change in inhibin-alpha subunit mRNA levels per testis corresponded to an approximately 3-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Production and regulation of inhibin subunits in pituitary gonadotropes.

Two related proteins, inhibin and activin, are produced and secreted by the gonads and act at the pituitary to regulate FSH secretion. In the present study, the alpha and beta B, but not the beta A, polypeptide subunits of inhibin were localized in the cytoplasm of FSH- and LH-immunoreactive (ir) gonadotropes. Ovariectomy (OVX) increased the size and number of cells immunoreactive for inhibin-alpha and -beta B as well as the mRNAs encoding these subunits. Treatment with estrogen prevented these effects. These results suggest that pituitary gonadotropes are sources, as well as targets, of inhibin-related peptides, whose expression in the pituitary is modulated by ovarian factors.

Animals↗

Differential production and regulation of inhibin subunits in rat testicular cell types.

The distributions of the alpha-, beta A-, and beta B subunits of inhibin/activin polypeptides were studied in the testis of adult (60-day-old) and immature (12-day-old) rats. Immunohistochemical techniques using antisera selective for each subunit were used to localize the polypeptide chains. In situ hybridization using radiolabeled complementary RNA probes enabled localization of the messenger RNAs (mRNAs) encoding these subunits. In 12-day-old rats, immunostaining and mRNA signal for the alpha-subunit was found in Leydig cell clusters. The beta A- and beta B-subunit staining and beta A-subunit message were detectable in isolated interstitial cells, but the clusters appeared to lack these subunits. Positive immunostaining for each subunit was localized in a Sertoli cell-like pattern in seminiferous tubules, as was a positive mRNA signal for the alpha- and beta B-subunit over regions containing these cell types. Treatment with human CG (hCG) and PMSG greatly enhanced the production of the alpha-subunit in the Leydig cell clusters, but not within the tubules, of these young rats. In adult rats, alpha- and beta B-subunit staining, and alpha-subunit mRNA signal, was observed in the interstitial cells. As in the immature animals, all three subunits were localized in a Sertoli cell-like pattern in the tubules, and a positive mRNA signal for the alpha- and beta B-subunits was found over these cells. There was, however, no obvious change in the expression of the subunits in the testis of adult rats after gonadotropin treatment. The present findings suggest that: 1) in the rat testis, both Sertoli and interstitial cells produce inhibin/activin subunits; 2) the alpha- and beta-subunits are produced by different types of interstitial cells in immature rats; and 3) the production of the alpha-subunit in the Leydig cells of immature rats is regulated by LH-like hormones.

Animals↗

Periovulatory changes in the expression of inhibin alpha-, beta A-, and beta B-subunits in hormonally induced immature female rats.

Immature female rats were treated with PMSG and human CG to induce ovulation. Sequential treatment with these hormones allowed us to investigate variations in the production of inhibin subunits shortly before ovulation and during the induced luteal phase. Using this model, we found that expression patterns for the alpha-, beta A-, and beta B-subunits were similar to those observed in mature cycling animals: administration of PMSG (to mimic the gonadotropin surge) led to a sharp increase in the expression of all three subunits in large preovulatory follicles whereas injection with human CG (to induce ovulation) caused a decrease in the levels of the respective mRNAs. In contrast to mature females, shortly before ovulation, levels of inhibin alpha-subunit mRNA were low in small antral follicles (approximately 350 microns). In addition, at that time, inhibin beta A- and beta B-subunits mRNAs were present in several large follicles (greater than 500 microns). More than 2 days after ovulation, inhibin beta A- and beta B-subunit mRNAs could not be detected in small antral size follicles (approximately 350 microns) of hormonally induced females. On the other hand, hybridization signals for the inhibin alpha-subunit were observed in some small antral and preantral size follicles, while signals were very low or undetectable in a large number of atretic follicles. Using this synchronized ovulation model, hybridization patterns for inhibin beta A-subunit mRNA was observed in interstitial cells, 8-10 h after ovulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gonadal and extragonadal expression of inhibin alpha, beta A, and beta B subunits in various tissues predicts diverse functions.

The S1-nuclease analysis was used to investigate the pattern of inhibin expression in the rat. In a first series of experiments, expression of the alpha, beta A, and beta B subunits of inhibin were monitored in various tissues from male and female rats. Two observations emerge from these studies. First, expression of inhibin subunits was found in gonadal and extragonadal tissues. In addition to the ovary and testis, inhibin alpha, beta A, and beta B RNAs were detected in the placenta, pituitary, adrenal, bone marrow, kidney, spinal cord, and brain. Detection of inhibin RNAs in the brain and spinal cord suggested that these subunits may exert neuroregulatory functions in the central and peripheral nervous systems. Furthermore, the presence of inhibin alpha and beta subunits in the placenta and the pituitary gland, two cell types that have clearly been shown to be regulated by exogenous inhibin, may reflect existing paracrine and/or autocrine processes active in these tissues. The second observation is that expression of inhibin subunit RNAs may vary by severalfold in a tissue-specific fashion. for example, alpha-subunit RNA levels are abundant in the gonads, whereas beta A-subunit RNA is predominant in the placenta and bone marrow. Finally, it is noted that expression of testicular inhibin RNA subunits decreases during sexual maturation. We conclude that the dimers comprised of inhibin subunits possess diverse functions and may act as growth/differentiation factors as well as a hormone.

Animals↗

Rapid changes in the expression of inhibin alpha-, beta A-, and beta B-subunits in ovarian cell types during the rat estrous cycle.

Distributions of inhibin alpha-, beta A-, and beta B-subunits in different ovarian compartments were studied in cycling female rats by in situ hybridization with complementary RNA probes and using immunohistochemical localization with antibodies selective for each inhibin subunit. Consistent with earlier studies showing inhibin production by granulosa cells of maturing follicles, we also detected mRNAs for inhibin alpha-, beta A-, and beta B-subunits in granulosa cells of these follicles. However, based on immunohistochemistry and in situ hybridization, we found that inhibin alpha- is not only expressed in granulosa cells of mature follicles but in follicles at all stages of maturation, including primary to tertiary follicles. A number of primordial follicles also contained alpha mRNA and immunodetectable alpha-subunit. Interestingly, theca interna and interstitial gland cells contained inhibin alpha mRNA and alpha-subunit. Low levels of inhibin alpha immunoreactivity as well as specific hybridization to the complementary inhibin alpha mRNA probe were observed in newly formed luteal tissue. beta-Subunits, on the other hand, were detected exclusively in granulosa cells of healthy tertiary follicles. The changes in expression of inhibin alpha-, beta A-, and beta B-subunits were more pronounced during the follicular phase of the cycle: inhibin alpha reached its highest level in granulosa cells, theca interna, and interstitial gland cells a few hours after the LH/FSH surge, while at the same time the beta-subunits decreased dramatically in granulosa cells of mature follicles. Immediately before ovulation (estrus 0200 h), the alpha-subunit sharply declined in preovulatory follicles and was present mainly in granulosa cells from nonovulatory follicles at various stages of maturation. At that time, the beta A- and beta B-subunits could not be detected in preovulatory follicles but were localized mainly in small tertiary follicles (less than 300 microns). Unlike for the alpha- and beta B-subunits, beta A mRNA and immunoreactivity was present in large tertiary follicles (approximately 600 microns) immediately before ovulation. The present findings support the hypothesis that a decrease in inhibin production could be responsible for the secondary FSH surge observed early on estrus. This could be initiated by a change in the ratios of activin-inhibin production by decreasing first, the levels of beta-subunits, second, the levels of alpha-subunit, and third, by a resurgence of activin A produced mainly by granulosa cells from large tertiary follicles.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗