Searchable abstracts of presentations at key conferences in endocrinology

ea0005p195 | Reproduction | BES2003

Oxygen tension regulates placental 11beta-hydroxysteroid dehydrogenase type 2

Driver P , Hewison M , Kilby M , Stewart P

In humans the most abundant source of 11 beta-hydroxysteroid dehydrogenase type 2 is the placenta, notably placental trophoblast. This enzyme catalyses the conversion of cortisol (F) to cortisone (E) and is thought to protect the fetus from maternal hypercortisolaemia, thereby impacting on fetal growth and development. During gestation placental trophoblast is exposed to dramatic changes in oxygen tensions ranging from ~2% - 12%, changes thought to be pivotal in stimulating an...

ea0003p221 | Reproduction | BES2002

Oxygen tension regulates placental 11 beta-hydroxysteroid dehydrogenase type 2

Driver P , Hewison M , Kilby M , Stewart P

11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is responsible for the conversion of hormonally active cortisol (F) to inactive cortisone (E), and is expressed in mineralocorticoid target tissues (kidney, colon). However, the most abundant source of this enzyme is human placenta, notably placental trophoblast where it is thought to protect the fetus from maternal hypercortisolaemia and play a role in fetal growth and development. During gestation placental trophobla...

ea0009oc10 | Oral Communication 2: Reproduction and growth | BES2005

Glucocorticoid-induced apoptosis in human decidua: a novel role for 11 beta-hydroxysteroid dehydrogenase in late gestation

Chan J , Evans K , Innes B , Bulmer J , Stewart P , Hewison M , Kilby M

Glucocorticoids (GCs) play a fundamental role in the endocrinology of pregnancy but excess GC in utero may lead to IUGR. Protection against fetal exposure to GCs is provided by the enzyme 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) located in the placental trophoblast. By contrast, relatively little is known concerning the function of GC-activating 11beta-HSD1 which is expressed within maternal decidua. We have used human deciduas (n=32 first, n=10 second and n=...

ea0005p164 | Growth and Development | BES2003

A potential role for human securin/PTTG in the developing human fetal brain

Boelaert K , McCabe C , Tannahill L , Bulmer J , Chan S , Gittoes N , Sheppard M , Kilby M , Franklyn J

Human securin, known also as pituitary tumor transforming gene (PTTG), has established oncogenic and cell regulatory functions. PTTG transforms cells in vitro, inhibits sister chromatid separation and regulates secretion of fibroblast growth factor-2 (FGF-2). FGF-2 is a key regulator of CNS development and PTTG/securin expression has previously been reported in murine fetal brain. We examined mRNA and protein expression of PTTG and FGF-2 in 35 first trimester (7-12 weeks) and ...

ea0003s32 | Parturition and Fetal Stress - Hormonal Strategies for Ensuring Life After Birth | BES2002

Thyroid hormone in the fetal brain

Kilby M

Thyroid hormones are known to be important for optimal development of the human central nervous system. Classically, maternal thyroid hormones have not been thought to play a major role in defining central nervous system development. However, recent epidemiological evidence has indicated that subtle deficiencies in circulating maternal thyroid hormones in the first trimester of pregnancy are associated with adverse neurodevelopment.We have used real-tim...

ea0029s10.1 | Thyroid: From fetal life to adulthood | ICEECE2012

Placental transport of thyroid hormone

Franklyn J. , Chan S. , Vasilopolou E. , Kilby M.

The transplacental passage of thyroid hormones (TH) from the maternal to fetal circulations is important for normal fetal development, particularly the fetal central nervous system. This is particularly so before the onset of endogenous fetal TH production from the second trimester of pregnancy. The human hemochorial placenta regulates the quantity of TH passing through and the complement of the different forms of TH to ensure requisite levels are present in the fetus for each...

ea0009p62 | Growth and development | BES2005

Separase and Securin; their roles in the developing human fetal brain

Pemberton H , Boelaert K , Kilby M , Franklyn J , McCabe C

During mitosis, temporal release of separase from its inhibitor securin results in cohesin cleavage, thereby promoting anaphase. The developing fetal brain has rapidly proliferating neuronal cells whilst adult neurons no longer proliferate. When comparing 61 fetal and 12 adult human brain samples, we found significantly increased separase mRNA and protein throughout ontogeny and reduced securin expression in fetal brain compared with adult. Using MTT assays, we examined the ef...

ea0007oc3 | Reproduction | BES2004

Decidual activation of vitamin D3 - a novel immunomodulatory mechanism in early gestation

Evans K , Innes B , Bulmer J , Kilby M , Hewison M

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D3) is a potent antiproliferative/immunomodulatory steroid hormone with many applications outside calcium homeostasis. This is particularly true in the placenta which can generate 1,25D3 locally via the enzyme 1alpha-hydroxylase (CYP27b) in both trophoblast and decidua. We have investigated the potential function of 1,25D3 across gestation using human tissue obtained after l...

ea0007p138 | Growth and development | BES2004

A dominant negative thyroid hormone receptor (TR) beta1 mutant enhances N-Tera-2 (NT2) cell proliferation

Chan S , McCabe C , Franklyn J , Kilby M

The vulnerability of early central nervous system (CNS) development to thyroid hormone (TH) deprivation has been highlighted by studies showing an association between maternal hypothyroxinemia during the first trimester and long-term neurodevelopmental delay in the offspring. The molecular mechanisms underlying this observation are, however, poorly understood. It is known that the actions of triiodothyronine (T3), the active TH metabolite, are primarily mediated by TRs, which ...

ea0005p116 | Endocrine Tumours and Neoplasia | BES2003

Dysregulated extra-renal synthesis of 1,25-dihydroxyvitamin D3: A novel cause of hypercalcemia associated with ovarian dysgerminomas

Evans K , Zehnder D , Kilby M , Taylor H , Hewison M

Hypercalcaemia is a prevalent complication in malignancies as a consequence of tumor secretion of parathyroid hormone related peptide (PTHrP). This complication is also associated with ovarian dysgerminomas but is much less common than for other tumours. To investigate this further we have studied 10 cases of dysgerminoma, assessing biochemical parameters and analysing mRNA and protein expression in tissue biopsies. Pathological reports show raised serum calcium and 1,25(OH)<s...