Endocrine Abstracts

Childhood hypothyroidism results in delayed skeletal maturation and impaired growth. Thyroid hormones act via thyroid hormone receptors α (TRα) and TRβ which are tempo-spatially regulated. In the skeleton, TRα is the predominant receptor, thus we hypothesise that the skeletal effects of hypothyroidism are mediated by TRα. To investigate this we assessed the response of wild type (wt), TRα knockout (TRα0/0) and TRβ knockout (TR...

Increased hypothalamic–pituitary–thyroid (HPT) axis activity results in high bone turnover. T3 stimulates osteoblast and osteoclast activities, whereas TSH is proposed to inhibit bone turnover directly. Resolving the relative importance of T3 and TSH is complicated by their physiological inverse relationship. We studied 10 controls and 4 patients with resistance to thyroid hormone (RTH), in which mutation of thyroid hormone receptor beta (THR...

Seasonal reproduction enables animals outside tropical regions to rear offspring in a favourable environment. Increasing day length triggers a hypothalamic relay involving thyrotropin, the type 2 deiodinase enzyme and thyroid hormone, which activates the hypothalamic-pituitary-gonadal axis to induce reproductive competence. Photoperiod regulates calcium metabolism and the egg-laying cycle in the Japanese quail (Coturnix japonica), and we hypothesised that activity of ...

Seasonal reproduction enables animals outside tropical regions to rear offspring in a favourable environment. Increasing day length triggers a hypothalamic relay involving thyrotropin, the type 2 deiodinase enzyme and thyroid hormone, which activates the hypothalamic-pituitary-gonadal axis to induce reproductive competence. Photoperiod regulates calcium metabolism and the egg-laying cycle in the Japanese quail (Coturnix japonica), and we hypothesised that activity of ...

The type 3 deiodinase enzyme (D3) inactivates T3 and prevents activation of T4 to protect the fetus from premature exposure to thyroid hormones. Rapidly falling levels of D3 activity and rising levels of T3 at birth initiate the onset of cell differentiation and organ maturation during the post-natal period. Congenital hypothyroidism causes delayed ossification with reduced bone mineral deposition and short stature. We hypothesize that increase...

Similar to thyroid hormones, the calcineurin/NFAT pathway regulates bone mass via its actions in osteoblasts and by indirect effects on osteoclast function. Calcineurin is a calcium- and calmodulin-activated phosphatase that dephosphorylates the transcription factor NFAT enabling its translocation to the nucleus. RCAN2 is an inhibitor of calcineurin that is stimulated by T3 in brain, heart and skeletal muscle although its expression in bone has not been studied. Thu...

MEN2B is the most aggressive form of MEN2. Consequently, the new American Thyroid Association guidelines recommend prophylactic thyroidectomy early in the first year of life. Ninety-seven percentage of MEN2B cases result from a germline methionine to threonine mutation at codon 918 (M918T) of the RET proto-oncogene. In addition, an exceedingly rare alanine to phenylalanine mutation at codon 883 (A883F) has been reported in 4 unrelated adults. In each case metastatic MTC and th...

A 30-year-old lady was transferred to our hospital at 37 weeks of pregnancy. Hypertension was noted at 24 weeks of gestation and managed with methyldopa and labetalol. Despite treatment, BP was labile with a systolic of 90–220 and diastolic of 50–129 mmHg. She reported occasional palpitations but not chest pain or shortness of breath. The patient had a history of migrainous headaches but not hypertension prior to pregnancy. Her brother had previously had an operation...

The hypothalamo-pituitary–thyroid (HPT) axis maintains controlled systemic levels of thyroid hormone (TH). This is achieved through negative feedback via the hypothalamic arcuate and paraventricular nuclei. The effects of thyroid hormone in other hypothalamic nuclei are yet to be elucidated. Administration of triiodothyronine (T3, thyroid hormone) into the hypothalamic ventromedial nucleus (VMN) increases food intake in rats. Thyroid hormone activation and inac...

G-protein subunit α-11 (Gα11), which is encoded by GNA11, plays a major role in calcium homeostasis by regulating parathyroid hormone (PTH) secretion, and germline loss-of-function mutations cause familial hypocalciuric hypercalcaemia type 2 (FHH2). Since Gα11 is ubiquitously expressed, we investigated whether FHH2 is associated with additional non-calcitropic phenotypes by analysing mice harbouring a homozygous germline deletion o...