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Biomedical subjects

S C Low

Publications and source records attributed to S C Low.

At least 19 recordsLinked to original sources
PubMed2005

Oral and pulmonary delivery of FSH-Fc fusion proteins via neonatal Fc receptor-mediated transcytosis.

BACKGROUND: The alpha and beta subunits of FSH were fused to the Fc domain of IgG1 either in a single chain or a heterodimer format. These molecules were absorbed through the epithelium in lung and intestine by neonatal Fc receptor (FcRn)-mediated transcytosis. METHODS AND RESULTS: Single chain and heterodimer FSH-Fc were made recombinantly in Chinese hamster ovary cells. Treatment of rats with a single s.c. dose of single chain or heterodimer FSH-Fc resulted in greater stimulation of ovarian weight (20.8+/-3.9 and 26.9+/-6.1 mg respectively) compared to those receiving vehicle (12.1+/-1.0 mg) or an equimolar dose of recombinant human FSH (14.3+/-1.7 mg). Both FSH-Fc fusion proteins were absorbed after oral dosing of newborn rats with long terminal half-lives of approximately 60 h, and pulmonary delivery in four cynomolgus monkeys produced maximum serum concentrations between 69 and 131 ng/ml with long terminal half-lives between 55 and 210 h. Serum inhibin levels increased after pulmonary dosing with single chain FSH-Fc (1.3- and 1.4-fold) and heterodimer FSH-Fc (5.9- and 7.1-fold) and remained elevated for >12 days after treatment with heterodimer FSH-Fc. CONCLUSIONS: We have shown that FSH-Fc fusion proteins have increased stability in blood and improved bioactivity in vivo, and that heterodimer FSH-Fc is more active in rats and monkeys than single chain FSH-Fc. These data suggest that Fc fusion proteins offer the potential for oral and pulmonary delivery of FSH.

Administration, Oral↗
PubMed2001

Selenocysteine incorporation directed from the 3'UTR: characterization of eukaryotic EFsec and mechanistic implications.

The mechanism of selenocysteine incorporation in eukaryotes has been assumed for almost a decade to be inherently different from that in prokaryotes, due to differences in the architecture of selenoprotein mRNAs in the two kingdoms. After extensive efforts in a number of laboratories spanning the same time frame, some of the essential differences between these mechanisms are finally being revealed, through identification of the factors catalyzing cotranslational selenocysteine insertion in eukaryotes. A single factor in prokaryotes recognizes both the selenoprotein mRNA, via sequences in the coding region, and the unique selenocysteyl-tRNA, via both its secondary structure and amino acid. The corresponding functions in eukaryotes are conferred by two distinct but interacting factors, one recognizing the mRNA, via structures in the 3' untranslated region, and the second recognizing the tRNA. Now, with these factors in hand, crucial questions about the mechanistic details and efficiency of this intriguing process can begin to be addressed.

3' Untranslated Regions↗
PubMed2001

Breast reconstruction after mastectomy: a survey of general surgeons in Singapore.

BACKGROUND: Breast cancer is the leading malignancy among women in Singapore. In the West as many as 30% of eligible patients undergo some form of reconstruction, but in Singapore breast reconstruction is not often performed. METHODS: A postal survey of general surgeons in Singapore (response rate of 46%) was conducted to ascertain the factors influencing their decision to refer for reconstruction and the possible concerns they had about reconstruction. RESULTS: Age, anticipated psychosocial morbidity and the need for adjuvant therapy were the most important factors identified. The survey also found that almost 30% of respondents were unsure of whether reconstruction would mask recurrence. Despite this, almost 80% of respondents felt that reconstruction was worth the effort, but 55% (compared to less than 20% in the West) felt that patients did not want reconstruction despite being advised of its availability. CONCLUSION: Lack of information and the perception that patients would not want reconstruction may be important reasons for the low emphasis placed on the role of breast reconstruction in post-mastectomy patients.

Age Factors↗
PubMed2000

SECIS-SBP2 interactions dictate selenocysteine incorporation efficiency and selenoprotein hierarchy.

Selenocysteine incorporation at UGA codons requires cis-acting mRNA secondary structures and several specialized trans-acting factors. The latter include a selenocysteine-specific tRNA, an elongation factor specific for this tRNA and a SECIS-binding protein, SBP2, which recruits the elongation factor to the selenoprotein mRNA. Overexpression of selenoprotein mRNAs in transfected cells results in inefficient selenocysteine incorporation due to limitation of one or more of these factors. Using a transfection-based competition assay employing overexpression of selenoprotein mRNAs to compete for selenoprotein synthesis, we investigated the ability of the trans-acting factors to overcome competition and restore selenocysteine incorporation. We report that co-expression of SBP2 overcomes the limitation produced by selenoprotein mRNA overexpression, whereas selenocysteyl-tRNA and the selenocysteine-specific elongation factor do not. Competition studies indicate that once bound to SECIS elements, SBP2 does not readily exchange between them. Finally, we show that SBP2 preferentially stimulates incorporation directed by the seleno protein P and phospholipid hydroperoxide glutathione peroxidase SECIS elements over those of other selenoproteins. The mechanistic implications of these findings for the hierarchy of selenoprotein synthesis and nonsense-mediated decay are discussed.

Cell Line↗
PubMed2000

Pathologic-radiologic correlations in screen-detected ductal carcinoma in situ of the breast: findings of the Singapore breast screening project.

Mammography detected 34 (25%) cases of ductal carcinoma in situ (DCIS) of the breast out of a total of 135 cancers diagnosed in 28, 231 participating women during the Singapore breast screening project. Radiologic findings in these 34 women with DCIS were calcifications only in 25 (74%); mass only in 2 (6%); and mass with calcifications in the remaining 7 (20%) cases. Calcifications were classified mammographically as powderish in 2 (6%), crushed stone-like in 16 (50%) and casting in 14 (44%) cases. Pathologic assessment revealed 11 (32%) cases with pure comedo, 16 (47%) mixed, 3 (9%) cribriform, 2 (6%) papillary, 1 (3%) micropapillary and 1 (3%) solid patterns. Histologic nuclear grade was low in 6 (18%), intermediate in 9 (26%) and high in 19 (56%). Necrosis was observed in 26 (77%) cases and absent in the rest. Pathologic-radiologic correlations yielded a significant association between the mammographic and pathologic lesional size, with the degree of agreement improved when there was histologic necrosis. A trend for radiologic crushed stone-like and casting-type calcifications to be associated with DCIS with necrosis and of higher nuclear grade was noted. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 231-236 (2000).

Aged↗
PubMed2000

Spectrum of abnormal mammographic findings and their predictive value for malignancy in Singaporean women from a population screening trial.

INTRODUCTION: The ability to categorise mammographic features according to their likelihood of malignancy would be valuable in the management of women with abnormal mammograms. The aim of our study was to correlate abnormal mammographic features in a screened population with their histology to identify those features which are predictive of malignancy. The study also examined the spectrum of mammographic features in an Asian population. MATERIALS AND METHOD: This prospective study involved 28,231 women who were randomly selected from a population registry and underwent two-view screening mammography without physical examination. Women with suspicious lesions were recalled for further mammographic views or to a joint assessment clinic prior to biopsy. Mammographic abnormalities and their corresponding histology were assessed. RESULTS: The spectrum of mammographic abnormalities was similar to that in Caucasian populations. The positive predictive value for malignancy was 44.1% of all biopsied cases. Mammographic features could be broadly classified into low-, moderate- and high-risk categories for malignancy. Those features which correspond to high malignancy rates (9.8% to 16.0%) include multiple abnormalities or parenchymal lesions with microcalcifications. The presence of microcalcifications was a good predictor of ductal carcinoma-in-situ (DCIS): 46% of lesions in which the microcalcifications were the sole abnormality were DCIS only. Further, 71% of cancers with any microcalcification on the mammogram had a focus of DCIS on histology. CONCLUSION: Mammographic abnormalities can be segregated into three risk groups for malignancy, and this in turn can improve the selection criteria for breast biopsy, hence reducing unnecessary intervention. Furthermore, the presence of microcalcifications denotes the presence of DCIS, and would be an important determinant of the extent of surgical excision.

Asian People↗
PubMed1999

Screen detected breast cancer in an Asian population: pathological findings of the Singapore breast screening project.

We document the pathological characteristics of 135 cancers detected in 132 predominantly Chinese women in the Singapore breast screening project. Thirty-four (25%) screen detected tumours were in situ ductal cancers; 98 (73%) invasive, while three (2%) women with malignant fine needle aspirate smears refused further treatment. The median size of in situ cancers was 10 mm; the majority (56%) demonstrated a comedo pattern. Of the invasive tumours which had a median size of 15 mm, three (3%) were microinvasive, 75 (77%) infiltrative ductal, three (3%) invasive lobular, and the remaining 17 (17%) special types or others. Histologic grading revealed 23 (24%) grade I, 52 (53%) grade II, 19 (19%) grade III and four (4%) ungraded cases. Sixty-three (65%) of the invasive cancers were node negative, while 64% of all screen detected malignancies were Stages 0 (in situ) or I. From the pathological perspective, problems of borderline lesions, microinvasion, grade assessment and histological subtyping have to be addressed.

Journal Article↗
PubMed1998

Results of intermediate measures from a population-based, randomized trial of mammographic screening prevalence and detection of breast carcinoma among Asian women: the Singapore Breast Screening Project.

BACKGROUND: Although increasing rates of breast carcinoma incidence have been observed in Asian countries, appropriate strategies for detecting early stage breast carcinoma in such communities have been difficult to formulate, particularly because no large population screening trial specifically involving Asian women has been reported. The objective of this study was to evaluate the effectiveness and quality of mammography as a screening technique for Singaporean women, who are predominantly Chinese. METHODS: In this prospective study, 166,600 women in Singapore ages 50-64 years were randomized to either 2-view mammography without physical examination (67,656) or observation (97,294, controls) over 2 years. RESULTS: Of these women, 28,231 (41.7%) responded and were screened; they were more likely to be married, have more formal education, be working, be Chinese, and be in a higher socioeconomic group (P < 0.001 for all variables). To assess for response bias that could affect outcome, results were also evaluated for nonrespondents (n = 39,425). The incidence rate of cancers among nonrespondents (1 per 1000 woman-years) was less than the 1.3 in women not invited to have screening (P = 0.03, relative risk [RR], 1.3; 95% confidence interval [CI], 1.0-1.7). However, cancers arising from nonrespondents did not differ significantly in stage distribution when compared with cancers within the control group. For every 1000 women screened, 4.8 cancers were detected. The prevalence ratio (the number of cancers detected per 1000 women at first screening divided by the corresponding incidence rate in controls per year) was 3.6 for screened women and 2.4 for women invited to have screening. The majority of cancers detected through screening were early stage, with 64% as either ductal carcinoma in situ (26%) or Stage I disease (38%) and was significantly more than the corresponding 26% in women not invited to have screening (P < 0.001). When only invasive cancers were considered, screened women still had more early cancers, with 65% having no lymph node involvement, compared with 47% in the group not invited to have screening (P = 0.001; RR, 1.4; 95% CI, 1.2-1.7). Women who were screened had half the risk of having Stage II or later cancers (P < 0.0001; RR, 0.5; 95% CI, 0.4-0.7) when compared with women not invited to have screening. This higher detection rate of early cancers through screening was accomplished with acceptable recall rates of 8% for further mammographic films or physical examination and a biopsy rate of 1.0% (10 per 1000 women screened). The interval cancer rate was 2.1 per 10,000 women screened in the first year of follow-up. CONCLUSIONS: These positive results of intermediate measures suggest that, in Asian communities, screening mammography could be an important modality for detecting early stage breast carcinoma. However, the low compliance rates suggest that health education efforts must focus on issues related to acceptability if such programs are to succeed.

Aged↗
PubMed1998

Non-operative treatment of breast abscesses.

BACKGROUND: Breast abscesses are conventionally treated by incision and drainage. This often requires general anaesthesia and a hospital stay. Non-operative treatment by needle aspiration and oral antibiotics is reported as a viable alternative. METHODS: All patients who presented with breast abscesses and who were assessed by one surgeon between November 1995 and January 1997 were managed using a conservative approach and they are the subjects of this study. RESULTS: Twenty-one consecutive patients were seen over a period of 26 months. All had non-lactational breast abscesses. Nineteen patients were successfully treated by needle aspiration and antibiotics while two patients required incision and drainage. The mean size of the aspirated abscesses was 3.5 cm (range 1-15 cm) and required an average of 2.4 aspirations (range 1-5). Of those treated by aspiration, three patients developed recurrent abscesses, two of which were successfully managed by repeat aspiration while one patient eventually required surgery. CONCLUSIONS: The majority of non-lactational breast abscesses seen in clinical practice can be treated without surgery by a combination of needle aspiration and antibiotics.

Abscess↗
PubMed1997

RNA and protein requirements for eukaryotic selenoprotein synthesis.

Selenium has been recognized as an essential nutrient in animals since the 1950s. Demonstration of the role of dietary selenium in protection from oxidative stress followed in the early 1970s, and was largely attributed to its presence as an integral part of cellular glutathione peroxidase. However, the functions of this enzyme did not explain many of the other effects of selenium deficiency. The identification of other mammalian selenoproteins during the last few years has provided new insights into the functions of this trace nutrient. The discovery that type 1 deiodinase (D1) is a selenoenzyme, in addition to unveiling an essential role for selenium in thyroid hormone action, has had more far-reaching implications. Studies of this protein opened the door for investigation of the requirements for eukaryotic selenoprotein synthesis, and the features that distinguish this pathway from the corresponding prokaryotic pathway. Selenium is present in a number of prokaryotic and eukaryotic proteins in the form of the unusual amino acid, selenocysteine. Incorporation of selenocysteine into these proteins requires a novel translation step in which UGA specifies selenocysteine insertion. Since UGA codons are typically recognized as translation stop signals, an intriguing question is raised: How does a cell recognize and distinguish a UGA selenocysteine codon from a UGA stop codon? In this review, we will focus on what is known about selenocysteine incorporation in eukaryotes, briefly summarizing initial studies and discussing a few recent advances in our understanding of this unique "recoding" process.

Animals↗
PubMed1996

Knowing when not to stop: selenocysteine incorporation in eukaryotes.

The regulation of translation frequently involves protein-RNA interactions. An intriguing example of this is the alternative decoding of UGA, typically a stop codon, as selenocysteine. Two RNA structures, the mRNA selenocysteine insertion sequence (SECIS element) and a unique selenocysteyl-tRNA, are required for this process. In prokaryotes, a single RNA-binding protein, a selenocysteine-specific elongation factor, interacts with both the tRNA and mRNA to confer decoding. Whether eukaryotes use a similar mechanism is currently the subject of intense investigation.

Base Sequence↗
PubMed1995

Cloning and functional characterization of human selenophosphate synthetase, an essential component of selenoprotein synthesis.

Selenocysteine is co-translationally incorporated into prokaryotic and eukaryotic selenoproteins at in-frame UGA codons. However, the only component of the eukaryotic selenocysteine incorporation machinery identified to date is the selenocysteine-specific tRNA(Sec). In prokaryotes, selenocysteine is synthesized from seryl-tRNA(Sec) and the active selenium donor, selenophosphate. Selenophosphate is synthesized from selenide and ATP by the selD gene product, selenophosphate synthetase, and is required for selenocysteine synthesis and incorporation into bacterial selenoproteins. We have now cloned human selD and shown that transfection of the human selD cDNA into mammalian cells results in increased selenium labeling of a mammalian selenoprotein, type 1 iodothyronine deiodinase. Despite significant differences between the mechanisms of selenoprotein synthesis in prokaryotes and eukaryotes, human selD weakly complements a bacterial selD mutation, partially restoring selenium incorporation into bacterial selenoproteins. Human selenophosphate synthetase has only 32% homology with the bacterial protein, although a highly homologous region that has similarity to a consensus ATP/GTP binding domain has been identified. Point mutations within this region result in decreased incorporation of selenium into type 1 iodothyronine deiodinase in all but one case. Further analysis revealed that reduced selenium labeling was due to altered ATP binding properties of the mutant selenophosphate synthetases.

Adenosine Triphosphate↗
PubMed1995

Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme.

Type 3 iodothyronine deiodinase (D3) catalyzes the conversion of T4 and T3 to inactive metabolites. It is highly expressed in placenta and thus can regulate circulating fetal thyroid hormone concentrations throughout gestation. We have cloned and expressed a 2.1-kb human placental D3 cDNA which encodes a 32-kD protein with a Km of 1.2 nM for 5 deiodination of T3 and 340 nM for 5' deiodination of reverse T3. The reaction requires DTT and is not inhibited by 6n-propylthiouracil. We quantitated transiently expressed D3 by specifically labeling the protein with bromoacetyl [125I]T3. The Kcat/Km ratio for 5 deiodination of T3 was over 1,000-fold that for 5' deiodination of reverse T3. Human D3 is a selenoenzyme as evidenced by (a) the presence of an in frame UGA codon at position 144, (b) the synthesis of a 32-kD 75Se-labeled protein in D3 cDNA transfected cells, and (c) the presence of a selenocysteine insertion sequence element in the 3' untranslated region of the mRNA which is required for its expression. The D3 selenocysteine insertion sequence element is more potent than that in the type 1 deiodinase or glutathione peroxidase gene, suggesting a high priority for selenocysteine incorporation into this enzyme. The conservation of this enzyme from Xenopus laevis tadpoles to humans implies an essential role for regulation of thyroid hormone inactivation during embryological development.

Amino Acid Sequence↗
PubMed1994

Glucocorticoids regulate hippocampal 11 beta-hydroxysteroid dehydrogenase activity and gene expression in vivo in the rat.

Chronic glucocorticoid excess or deficiency is associated with hippocampal dysfunction and neuronal death. 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD), which catalyses the reversible conversion of corticosterone to inactive 11-dehydrocorticosterone, regulates glucocorticoid access to receptors in the kidney and liver in vivo. The enzyme is also present in the hippocampus where it might modulate glucocorticoid action. We examined the effects of corticosteroid manipulations on hippocampal and peripheral 11 beta-OHSD. In the hippocampus, chronic adrenalectomy (10 days) had no effect on 11 beta-OHSD activity, compared to sham-operated controls. Treatment of adrenalectomized animals with dexamethasone (200 micrograms/kg.day-1), but not aldosterone (20 micrograms/kg.day-1), for 10 days significantly increased hippocampal 11 beta-OHSD activity compared with sham or adrenalectomized rats (22% and 23% rise respectively, P < 0.05). These effects reflect changes in transcription of the liver-type 11 beta-OHSD gene, with dexamethasone significantly increasing 11 beta-OHSD mRNA expression in the hippocampus compared with sham or adrenalectomized animals (32% and 70% higher respectively, P < 0.05). In the liver, adrenalectomy significantly reduced 11 beta-OHSD activity (16% lower), which was restored to sham levels by dexamethasone, but not aldosterone. Similar trends were seen in 11 beta-OHSD mRNA expression, although these did not reach significance. None of the manipulations altered 11 beta-OHSD activity or mRNA expression in the kidney. The hippocampal effects of dexamethasone were similar to those of chronic stress (arthritis) which increased 11 beta-OHSD activity (20% rise, P < 0.05), although this was not reflected at the level of mRNA. Thus, hippocampal (and hepatic, but not renal) 11 beta-OHSD appears to be regulated by chronic glucocorticoid manipulations and stress. Hippocampal 11 beta-OHSD may thus ensure optimal long-term corticosterone exposure of glucocorticoid-sensitive neurons.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

'Liver-type' 11 beta-hydroxysteroid dehydrogenase cDNA encodes reductase but not dehydrogenase activity in intact mammalian COS-7 cells.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the metabolism of corticosterone to inert 11-dehydrocorticosterone, thus preventing glucocorticoid access to otherwise non-selective renal mineralocorticoid receptors (MRs), producing aldosterone selectivity in vivo. At least two isoforms of 11 beta-HSD exist. One isoform (11 beta-HSD1) has been purified from rat liver and an encoding cDNA cloned from a rat liver library. Transfection of rat 11 beta-HSD1 cDNA into amphibian cells with a mineralocorticoid phenotype encodes 11 beta-reductase activity (activation of inert 11-dehydrocorticosterone) suggesting that 11 beta-HSD1 does not have the necessary properties to protect renal MRs from exposure to glucocorticoids. This function is likely to reside in a second 11 beta-HSD isoform. 11 beta-HSD1 is co-localized with glucocorticoid receptors (GRs) and may modulate glucocorticoid access to this receptor type. To examine the predominant direction of 11 beta-HSD1 activity in intact mammalian cells, and the possible role of 11 beta-HSD in regulating glucocorticoid access to GRs, we transfected rat 11 beta-HSD1 cDNA into a mammalian kidney-derived cell system (COS-7) which has little endogenous 11 beta-HSD activity or mRNA expression. Homogenates of COS-7 cells transfected with increasing amounts of 11 beta-HSD cDNA exhibited a dose-related increase in 11 beta-dehydrogenase activity. In contrast, intact cells did not convert corticosterone to 11-dehydrocorticosterone over 24 h, but showed a clear dose-related 11 beta-reductase activity, apparent within 4 h of addition of 11-dehydrocorticosterone to the medium.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Sexual dimorphism of hepatic 11 beta-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) catalyses the reversible metabolism of corticosterone to inert 11-dehydrocorticosterone. At least two isoforms exist. 11 beta-HSD-1, the first to be characterised and the only isoform for which a cDNA has been isolated, is highly expressed in liver, kidney and hippocampus. The activity of 11 beta-HSD in rat liver is higher in males, due to oestrogen repression of 11 beta-HSD-1 gene transcription in females. Sexual dimorphism in rodent liver proteins is frequently mediated indirectly via sex-specific patterns of GH release (continuous in females, pulsatile in males). We have now investigated whether this applies to 11 beta-HSD, using dwarf rats (congenitally deficient in GH) and hypophysectomised animals. 11 beta-HSD activity and 11 beta-HSD-1 mRNA expression in liver was significantly lower in control female than male rats (50% and 72% of male levels respectively). These sex differences in the liver were attenuated in dwarf rats, with both males and females showing similar levels of 11 beta-HSD activity to control males. Administration of continuous (female pattern) GH to dwarf male rats decreased hepatic 11 beta-HSD activity (30% fall) and mRNA expression (77% fall), whereas the same total daily dose of GH given in the male (pulsatile) pattern had no effect on hepatic 11 beta-HSD in female dwarf rats. Continuous GH also attenuated hepatic 11 beta-HSD activity (25% fall) and 11 beta-HSD-1 mRNA expression (82% fall) in hypophysectomised animals.(ABSTRACT TRUNCATED AT 250 WORDS)

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1993

The 11 beta-hydroxysteroid dehydrogenase inhibitor glycyrrhetinic acid affects corticosteroid feedback regulation of hypothalamic corticotrophin-releasing peptides in rats.

Steroid-metabolizing enzymes modulate the effects of androgens on brain differentiation and function, but no similar enzymatic system has been demonstrated for adrenocorticosteroids which exert feedback control on the hypothalamus. 11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) rapidly metabolizes physiological glucocorticoids (corticosterone, cortisol) to inactive products, thereby regulating glucocorticoid access to peripheral mineralocorticoid and glucocorticoid receptors in a site-specific manner. Using in-situ hybridization, we found expression of 11 beta-OHSD mRNA in neurones of the hypothalamic paraventricular nucleus (PVN) where corticotrophin-releasing factor-41 (CRF-41) is synthesized and from where it is released into hypophysial portal blood. Administration of glycyrrhetinic acid (GE), a potent 11 beta-OHSD inhibitor, decreased CRF-41 release into hypophysial portal blood in the presence of unchanged circulating glucocorticoid levels, suggesting that 11 beta-OHSD regulates the effective corticosterone feedback signal to CRF-41 neurones. These effects of GE were not observed in adrenalectomized animals, demonstrating dependence on adrenal products. In contrast, GE led to two- to threefold increases in arginine vasopressin and oxytocin release into portal blood, effects also dependent upon intact adrenal glands. These results suggest that 11 beta-OHSD in the PVN, and possibly other sites, may represent a novel and important control point of corticosteroid feedback on CRF-41 release in vivo.

11-beta-Hydroxysteroid Dehydrogenases↗