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Neuroendocrinology. 2002 Oct;76(4):243-53.
Altered control of the hypothalamo-pituitary-adrenal axis in adult male rats exposed perinatally to food deprivation and/or dehydration.

Sebaai N, Lesage J, Vieau D, Alaoui A, Dupouy JP, Deloof S.

Laboratoire de Neuroendocrinologie du Developpement, UPRES-EA 2701, Universite de Lille 1, Villeneuve d'Ascq, France.

Dehydration, a classic homeostatic stressor in rats, leads to a series of well characterized endocrine responses including stimulation of the hypothalamo-pituitary-adrenal (HPA) axis. In this study, the hypothesis to be tested was that a 50% maternal food restriction (FR50) in late gestation and lactation may have long-term repercussions on HPA axis responsiveness to dehydration in offspring. For this purpose, we studied HPA axis activity in 4-month-old control (C) and perinatally malnourished male rats after a 72-hour water deprivation period. Furthermore, we investigated the long-lasting effects of perinatal maternal malnutrition on the basal activity of the HPA axis. Under basal conditions, rats exposed to perinatal malnutrition showed reduced body weight, enhanced mineralocorticoid receptor (MR) mRNA levels in CA2 and CA3 hippocampal areas, but decreased glucocorticoid receptor (GR) mRNA levels in CA1, CA3 and dentate gyrus (DG) areas. In contrast, the levels of corticotropin-releasing hormone (CRH) and vasopressin (VP) mRNAs in the hypothalamic paraventricular nucleus (PVN) as well as of VP mRNA in the supraoptic nucleus (SON) were unaffected by maternal undernutrition. Expression of proopiomelanocortin (POMC) in the adenohypophysis was significantly enhanced, whereas prohormone convertase-1 (PC1) was not affected. Perinatal malnutrition reduced absolute adrenal weight but did not affect circulating levels of adrenocorticotropin (ACTH), corticosterone and free corticosterone as well as corticosteroid-binding globulin (CBG) binding capacity. Seventy-two hours of dehydration induced a decrease in body weight and CRH mRNA levels in PVN of controls as well as of FR50 rats, but also led to a rise in plasma corticosterone and free corticosterone without changing CBG binding capacity. Dehydration also induced an increase in adenopituitary POMC (C) and PC1 (FR50), PVN and SON VP (C) and GR in CA1 hippocampal area (FR50) mRNA levels and plasma ACTH (C), but a decrease in MR in DG (C) and GR in CA3 and DG (C) mRNA levels. We conclude that maternal food restriction during the perinatal period affects (1) the adult basal activity of the HPA axis with mainly opposite effects on hippocampal MR and GR gene expression and an increase in adenopituitary POMC gene expression, and (2) the responsiveness to water deprivation in adults. In the latter case, the rise in plasma ACTH levels, adenopituitary POMC gene expression, hypothalamic VP gene expression, and the decrease in hippocampal MR gene expression in DG and GR gene expression in CA3 and DG observed in controls are lacking in FR50 rats. In contrast, drastic adenopituitary PC1 gene expression occurred in FR50 rats but not in control animals. 2002 S. Karger AG, Basel

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12411741&dopt=Abstract

Nephron Clin Pract. 2003 Jan;93(1):C21-8.
Abnormal vitamin D metabolism and loss of bone mass after renal transplantation.

de Sevaux RG, Hoitsma AJ, van Hoof HJ, Corstens FJ, Wetzels JF.

Department of Nephrology, University Medical Center, Nijmegen, The Netherlands. R.deSevauefro.azn.nl

BACKGROUND/AIM: Osteoporosis is a major complication after renal transplantation. The most important causative factor is the use of corticosteroids, but abnormalities in vitamin D metabolism and persisting hyperparathyroidism could also be involved. The present study examines changes in vitamin D metabolites, intact parathyroid hormone, and bone mineral density (BMD) during the first 2 years after renal transplantation. METHODS: Sixty-one patients (38 male, 23 female; age 42 +/- 13 years) who received a renal transplant participated in the study. Immunosuppressive treatment consisted of ciclosporin and prednisone. Laboratory parameters and BMD (lumbar spine and hip) were measured at baseline and 1 (laboratory only), 3, 6, 12, and 24 months after transplantation. RESULTS: At the time of transplantation, the 1,25-dihydroxyvitamin D levels were low in all patients. Although we observed a gradual increase, subnormal values were still present in 39 (64%) and 29 (47%) patients 3 and 6 months after transplantation, respectively. From 3 months after transplantation the 1,25-dihydroxyvitamin D level correlated with the creatinine clearance. After transplantation, the intact parathyroid hormone levels declined rapidly to values slightly above normal. The lumbar BMD was nearly normal at the time of transplantation, but decreased rapidly within 6 months (-6.5 +/- 4.5%; p < 0.001). A smaller decrease occurred in the femoral neck (-4.1 +/- 6.5%; p < 0.001), in Ward's triangle (-2.4 +/- 13.0%; p < 0.01), and in the trochanter (-5.1 +/- 6.3%; p < 0.001). After 6 months, the bone mass stabilized. CONCLUSIONS: The vitamin D metabolism remains disturbed for a considerable time after renal transplantation. In nearly half of the patients, the levels of active vitamin D remain abnormal for at least 6 months. The BMD decreased during the first 6 months after transplantation and remained stable thereafter. We speculate that the observed abnormalities in vitamin D metabolism may contribute to the early bone loss after renal transplantation. 2003 S. Karger AG, Basel

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12411755&dopt=Abstract

Dev Dyn. 2002 Nov;225(3):221-32.
Different patterns of anti-Mullerian hormone expression, as related to DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9 expression, in the chick differentiating gonads.

Oreal E, Mazaud S, Picard JY, Magre S, Carre-Eusebe D.

Unite de Recherches sur l'Endocrinologie du Developpement, INSERM U493, Ecole Normale Superieure, Montrouge, France.

In mammals, anti-Mullerian hormone (AMH) is produced by Sertoli cells from the onset of testicular differentiation and by granulosa cells after birth. In birds, AMH starts to be expressed in indifferent gonads of both sexes at a similar level and is later up-regulated in males. We previously demonstrated that, unlike in mammals, the onset of AMH expression occurs in chick embryo in the absence of SOX9. We looked for potential factors that might be involved in regulating AMH expression at different stages of chick gonad differentiation by comparing its expression pattern in embryos and young chicken with that of DMRT1, SF-1, WT1, GATA-4, Wnt-4, and Lhx9, by in situ hybridization. The results allowed us to distinguish different phases. (1) In indifferent gonads of both sexes, AMH is expressed in dispersed medullar cells. SF-1, WT1, GATA-4, Wnt-4, and DMRT1 are transcribed in the same region of the gonads, but none of these factors has an expression strictly coincident with that of AMH. Lhx9 is present only in the cortical area. (2) After this period, AMH is up-regulated in male gonads. The up-regulation is concomitant with the beginning of SOX9 expression and a sex dimorphic level of DMRT1 transcripts. It is followed by the aggregation of the AMH-positive cells (Sertoli cells) into testicular cords in which AMH is coexpressed with DMRT1, SF-1, WT1, GATA-4, and SOX9. (3) In the females, the low level of dispersed medullar AMH expression is conserved. With development of the cortex in the left ovary, cells expressing AMH accumulate in the juxtacortical part of the medulla, whereas they remain dispersed in the right ovary. At this stage, AMH expression is not strictly correlated with any of the studied factors. (4) After hatching, the organization of left ovarian cortex is characterized by the formation of follicles. Follicular cells express AMH in conjunction with SF-1, WT1, and GATA-4 and in the absence of SOX9, as in mammals. In addition, they express Lhx9 and Wnt-4, the latter being also found in the oocytes. (5) Moreover, unlike in mammals, the chicken ovary retains a dispersed AMH expression in cortical interstitial cells between the follicles, with no obvious correlation with any of the factors studied. Thus, the dispersed type of AMH expression in indifferent and female gonads appears to be bird-specific and not controlled by the same factors as testicular or follicular AMH transcription. 2002 Wiley-Liss, Inc.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12412004&dopt=Abstract

Mol Reprod Dev. 2002 Dec;63(4):444-50.
Inhibition of luteinizing hormone receptor expression during the development of caprine corpora lutea by administration of gonadotropin-releasing hormone antagonist.

Kawate N, Tsuji M, Tamada H, Inaba T, Sawada T.

Laboratory of Theriogenology, Graduate School of Agriculture and Biological Sciences, Osaka Prefecture University, Sakai, Osaka, Japan. nkawatet.osakafu-u.ac.jp

The present study was conducted to examine effects of a potent GnRH antagonist (GA), which suppresses release of luteinizing hormone (LH), on LH receptor expression during the development of the caprine corpus luteum (CL). Goats were divided into control and GA-treated groups. The goats were treated with saline or GA (50 microg/kg, s.c.) on days 0 (day of ovulation), 4 and 8 (control only), and CL collected on a subset of goats (n = 3 for each day) on days 0 (no saline), 4, 8, or 14 (control only). Ribonuclease protection assay and [(125)I]-hCG binding assay were performed to quantitate mRNA and protein of the LH receptor in the CL, respectively. On day 4, CL weight, levels of LH receptor mRNA and protein in the GA-treated group were similar to those of the control group. By day 8, CL weight and levels of LH receptor mRNA and protein in the GA-treated group were reduced relative to those of the control group (P < 0.05). There was no difference of affinity of the LH receptor between both groups on day 8. These results suggest that the treatment with GA inhibits gene and protein expressions of the LH receptor during the development of CL in the goat, and thus, support an idea that endogenous LH participates in the increase of its own receptor. 2002 Wiley-Liss, Inc.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12412046&dopt=Abstract [PubMed - in process]

Cancer. 2002 Nov 15;95(10):2068-75.
HER-2/neu status and tumor morphology of invasive breast carcinomas in Ashkenazi women with known BRCA1 mutation status in the Ontario Familial Breast Cancer Registry.

Quenneville LA, Phillips KA, Ozcelik H, Parkes RK, Knight JA, Goodwin PJ, Andrulis IL, O'Malley FP.

Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.

BACKGROUND: The prevalence of BRCA1 germline mutations is greater in the Ashkenazi Jewish population than in the general North American population. The Ontario Familial Breast Cancer Registry collects clinical and family history data in familial breast carcinoma cases, and unselected Ashkenazi breast carcinomas, and acts as a tumor tissue repository. METHODS: Using this resource, we examined the tumor morphology, hormone receptor status, and HER-2/neu protein overexpression in Canadian Ashkenazi breast carcinoma patients whose germline BRCA1 mutation status is known. RESULTS: Thirty-eight tumors from 32 BRCA1 carriers and 354 tumors from 334 noncarriers were analyzed.The tumors in BRCA1 mutation carriers were more likely to be high grade (P < 0.0001) and estrogen receptor negative (P < 0.004). There was an increased frequency of typical medullary carcinomas in mutation carriers when all tumors were analyzed. However, this difference did not remain statistically significant when only the first tumor diagnosed in each patient was included in the analysis. There was no difference in HER-2/neu protein overexpression between the two groups overall (P = 0.07). However, when the analysis was restricted to Grade III tumors, there were significantly fewer HER-2/neu-positive tumors in the mutation carriers versus noncarriers (3.1% vs. 21.5%, P = 0.012). No significant differences were found in the incidence of lymph node status, progesterone receptor status, lymphatic vessel invasion, degree of lymphocytic infiltration, or in the presence of ductal carcinoma in situ associated with the invasive tumors. CONCLUSIONS: Increasing awareness of the morphologic and immunophenotypic features more commonly found in BRCA1-associated breast carcinomas may lead to a wider use of these characteristics in genetic screening programs and provide further clues to their pathogenesis. 2002 American Cancer Society.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12412159&dopt=Abstract

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