Abstract

The influence of volume status on the effect of physiological doses of vasopressin on sodium excretion was assessed in anaesthetized Brattleboro rats. Following a 1 h control period, animals were divided into four groups. Group 1 (control) rats were kept in water balance throughout (by adjustment of the rate of i.v. glucose infusion) and received no vasopressin. In group 2 rats, vasopressin (20 μU/min) was infused i.v. for 2 h, then withdrawn during the following 2 h; the vasopressin-induced antidiuresis and subsequent return to water diuresis were matched by appropriate changes in the i.v. infusion, thus maintaining water balance. In this group, vasopressin had no effect on sodium excretion. Group 3 rats received the same dose of vasopressin, but the infusion rate of the glucose solution was not reduced; consequently these rats became water-loaded. In this group, sodium excretion increased significantly during vasopressin infusion, and rapidly returned to baseline values when the vasopressin was discontinued. Group 4 rats were treated in the same way as group 3 animals except that the vasopressin infusion was maintained (but without additional water loading) for a further 2 h; this did not prevent the fall in sodium excretion during the final 2 h of the experiment. We conclude that the natriuretic effect of physiological levels of vasopressin reported elsewhere may be dependent on an accompanying acute volume expansion during infusion of the hormone.

Journal of Endocrinology (1996) 151, 49–54

Studies in nonhuman primates indicate that changes in the thickness and integrity of the vaginal epithelium affect the transmission rates of HIV-1, but few studies have examined the normal variations that may occur in the vagina of normal macaques as a result of aging or changes in the menstrual cycle. This study was conducted to determine if differences occur in the thickness of the vaginal mucosa with age or menses. Vaginal mucosal thickness was compared in 46 rhesus macaques grouped as juvenile (1–3 years old), mature cycling (3–21 years old), and geriatric (> 21 years old). Epithelia of mature cycling macaques were also compared at different stages of the menstrual cycle. Older females (> 21 years) had the thinnest and least keratinized epithelium of all groups, followed by the youngest females (< 3 years). The vaginal epithelium was also thinner in cycling macaques during menses compared to the follicular stage. In addition, young, geriatric, or cycling macaques during menses had minimal keratinization. We hypothesize that normal physiologic changes in the vaginal epithelium of women occur with age and menses, which may affect a woman’s susceptibility to HIV-1 transmission and other sexually transmitted diseases. Also, age and menstrual cycle should be considered when designing vaginal transmission experiments in rhesus macaques.

ABSTRACT

Receptors for 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃) were prepared from bovine parathyroid glands and incubated with fragments of DNA of the 5′-flanking region of the bovine parathyroid hormone (PTH) gene covering 1700 base pairs (bp) upstream of the initiation site. In filter binding assays, incubation of the DNA fragment spanning − 700 to + 50 bp with 200 μg cytosolic protein gave 288±63% (mean ± s.d.) of binding in the absence of protein. In contrast, there was no significant reaction with the −1350 to − 700 bp fragment, nor was there binding of the receptor to a fragment of DNA covering the coding region of the PTH gene. Substitution of bovine serum albumin for the receptor preparation did not induce binding to the − 700 to + 50 bp fragment. The receptor-binding site was further defined to −700 to − 100 bp as deletion of the − 100 to + 50 bp did not reduce receptor binding.

Reaction of receptors further purified by sucrose density ultracentrifugation with a monoclonal antibody in immunoblots revealed a single species with a molecular mass of approximately 50 000 Da, which was absent in preparations of cos-1 cells. Autoradiography following incubation of receptors immobilized on nitrocellulose filters with the −700 to + 50 bp fragment indicated a single reactive band coincident with the band in the immunoblot. The DNA fragment did not bind to filters containing preparations of cos-1 cells. Extraction of the receptors in the presence or absence of 1,25-(OH)₂D₃ (4 nmol/l) or the presence of KCl (150 mmol/l) in the incubation medium had no significant effect on DNA binding to the protein in this assay.

Autoradiography following incubation of immobilized receptors with the −700 to +50 bp, −485 to −50 bp, −700 to −100 bp and −700 to −485 bp fragments revealed a binding site for the receptor for 1,25-(OH)₂D₃ between −485 and −100 bp upstream of the initiation site in the bovine PTH gene.

Journal of Endocrinology (1990) 126, 355–359

The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24–28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r ²=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development.