Maternal hypothyroidism decreases progesterone receptor expression in the cortical subplate of foetal rat brain.

Steroid hormones exert profound effects on the development of brain areas controlling complex cognitive function in adulthood. One class, progestins, may contribute by acting on the progestin receptor (PR), which is transiently expressed in a critical layer of developing cortex: the subplate. PR expression in the subplate coincides with the establishment of ongoing cortical connectivity and may play an important organisational role. Identification of the factor(s) that regulate the precise timing of PR expression within subplate may help elucidate the function of PR. Thyroid hormone may interact with hormone response elements within the PR gene. The present study examined the effects of maternal hypothyroidism on levels of PR immunoreactivity (PR-IR) within the foetal subplate. Pregnant rats were made hypothyroid by the administration of methimazole and potassium perchlorate in drinking water. Maternal hypothyroidism significantly decreased PR-IR within the foetal subplate. Using the incorporation of 5-bromo-2'-deoxyuridine (BrDU) during subplate cell neurogenesis (embryonic day 13.5) to determine subplate cell survival in hypothyroid animals, we found that decreases in PR-IR cannot be attributed to significant subplate cell loss but are more likely the result of altered PR expression. Gestational thyroxine replacement to hypothyroid dams prevented the decrease in PR-IR within the subplate. These results identify thyroid hormone as a potential factor in the regulation of PR expression in the developing brain. These results are consistent with the idea that endocrine cross-talk between progesterone and thyroid hormone may be one mechanism by which maternal hypothyroidism alters normal cortical development.

Multifactorial modulation of TRH metabolism.

1. Thyrotropin releasing hormone (TRH), synthesized in the paraventricular nucleus of the hypothalamus (PVN), is released in response to physiological stimuli through median eminence nerve terminals to control thyrotropin or prolactin secretion from the pituitary. 2. Several events participate in the metabolism of this neuropeptide: regulation of TRH biosynthesis and release as well as modulation of its inactivation by the target cell. 3. Upon a physiological stimulus such as cold stress or suckling, TRH is released and levels of TRH mRNA increase in a fast and transient manner in the PVN; a concomitant increase in cfos is observed only with cold exposure. 4. Hypothalamic cell cultures incubated with cAMP or phorbol esters show a rise in TRH mRNA levels; dexamethasone produces a further increase at short incubation times. TRH mRNA are thus controlled by transsynaptic and hormonal influences. 5. Once TRH is released, it is inactivated by a narrow specificity ectoenzyme, pyroglutamyl peptidase II (PPII). 6. In adenohypophysis, PPII is subject to stringent control: positive by thyroid hormones and negative by TRH; other hypothalamic factors such as dopamine and somatostatin also influence its activity. 7. These combined approaches suggest that TRH action is modulated in a coordinate fashion.

Neuroanatomical distribution of vasotocin in a urodele amphibian (Taricha granulosa) revealed by immunohistochemical and in situ hybridization techniques.

Immunohistochemical and in situ hybridization techniques were used to investigate the neuroanatomical distribution of arginine vasotocin-like systems in the roughskin newt (Taricha granulosa). Vasotocin-like-immunoreactive neuronal cell bodies were identified that, based on topographical position, most likely, are homologous to groups of vasopressin-immunoreactive neuronal cell bodies described in mammals, including those in the bed nucleus of the stria terminalis, medial amygdala, basal septal region, magnocellular basal forebrain-including the horizontal limb of the diagonal band of Broca, paraventricular and supraoptic nuclei, suprachiasmatic nucleus, and dorsomedial hypothalamic nucleus. Several additional vasotocin-like-immunoreactive cell groups were observed in the forebrain and brainstem regions; these observations are compared with previous studies of vasotocin- and vasopressin-like systems in vertebrates. Arginine vasotocin-like-immunoreactive fibers and presumed terminals also were widely distributed with high densities in the basal limbic forebrain, the ventral preoptic and hypothalamic regions, and the brainstem ventromedial tegmentum. Based on in situ hybridization studies with synthetic oligonucleotide probes for vasotocin and the related neuropeptide mesotocin, as well as double-labeling studies with combined immunohistochemistry and in situ hybridization, we conclude that the vasotocin immunohistochemical procedures used identify vasotocin-like, but not mesotocin-like, elements in the brain of T. granulosa. The distribution of arginine vasotocin-like systems in T. granulosa is greater than the distribution previously reported for any other single vertebrate species; however, it is consistent with an emerging pattern of distribution of vasotocin- and vasopressin-like peptides in vertebrates. Complexity in the vasotocinergic system adds further support to the conclusion that this peptide regulates multiple neurophysiological and neuroendocrinological functions.

Fatal hydrofluoric acid cutaneous exposure with refractory ventricular fibrillation.

A patient with hydrofluoric acid burns involving only 8% of his body surface area died from intractable cardiac arrhythmia secondary to the depletion of ionized calcium by fluoride ion. For burns of this type, immediate subcutaneous injection of 10% calcium gluconate into the burn wound is recommended and the dose given should be titrated to the relief of local pain. Immediate debridgement of the burn wound also can decrease the treacherous aspect of the circulating fluoride ion, which binds to calcium to form an insoluble salt, effectively removing the calcium ion from any physiologic interaction.