The specific retention of androgens and oestrogens by cytoplasmic components of human ovarian tumours was investigated. High-affinity, low-capacity binding of androgens was observed in 88% of tumour specimens and oestrogen binding in 32%. Retention of oestrogens did not occur in the absence of androgen binding. The androgen-binding component, of sedimentation coefficient 7·5–8·5S, showed specificity for 5α-dihydrotestosterone and 17β-hydroxy-17α-methyl-estra-4,9,11-trien-3-one (R1881). In some instances, competition for R1881-binding sites indicated the presence of progesterone receptor-like binding. The data presented suggest strongly the existence of androgen and oestrogen receptors in some ovarian tumours and may be relevant to histopathological classification and therapeutic rationales.
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T. C. HAMILTON, P. DAVIES, and K. GRIFFITHS
T. C. Hamilton, P. Davies, and K. Griffiths
The surface germinal epithelium of the rat ovary was isolated and grown in vitro. Cytosol from cultured cells contained a saturable component, of sedimentation coefficient 7·5–8·5S, which bound oestrogenic and antioestrogenic substances with high affinity (K d 400 pmol/l). Nuclei isolated from cells exposed to [3H]oestradiol contained radioactivity partially susceptible to KC1 extraction. Sedimentation analysis of the KC1 extract showed that [3H]oestradiol was associated with a moiety of sedimentation coefficient 4·5–5S.
R Braddock, CM Siman, K Hamilton, H Devlin, H Garland, and CP Sibley
Experimental diabetes in rats is associated with excessive electrolyte loss in the urine, which is further accentuated by pregnancy, particularly of Ca. Supplementation with essential fatty acids and antioxidants has proven beneficial in treating several types of complications, including nephropathy. The present study investigated the effect of gamma-linoleic acid (GLA; 500 mg/kg per day; group DG) and ascorbate (290 mg/kg per day; group DA), alone and in combination (group DGA), as well as ascorbyl-GLA (790 mg/kg per day; group DASG), on urinary electrolyte output and skeletal composition in pregnant streptozotocin-diabetic rats. Urine was collected in metabolism cages before and throughout pregnancy. Diabetic rats (DP) increased their urine volume as compared with control (CP) throughout the experiment, reaching an output of more than 13 times that of the control group by the end of pregnancy (CP 24+/-4, DP 316+/-21, DG 223+/-21, DA 221+/-14, DASG 163+/-17, DGA 220+/-19 ml urine/24 h). Concomitant with increased urine volume was a reduction of urinary Na (CP 47+/-14, DP 22+/-5 mmol/l), K (CP 210+/-34, DP 31+/-1 mmol/l) and Mg (CP 14+/-1, DP 3.8+/-0.2 mmol/l) concentration, but not of Ca concentration (CP 5.4+/-1.5, DP 6.3+/-0.6 mmol/l), and hence total Ca loss was relatively most severe. All the treatments reduced urine volume with no effects on electrolyte concentration as compared with DP, with no significant difference between the treatments. A reduced bone size and bone Ca content was partially ameliorated by the diet supplementation. We have concluded that GLA and ascorbate, alone or in combination, prevent urinary electrolyte loss in pregnant rats and do so by reducing urine production.
K Hamilton, M Tein, J Glazier, EB Mawer, JL Berry, RJ Balment, RD Boyd, HO Garland, and CP Sibley
Offspring of rats with diabetes mellitus are at risk of reduced calcium and bone mineral content. Altered expression of the maternal calcium binding proteins, calbindin-D(9K) and calbindin-D(28K), which are involved in renal and placental calcium transport, may underlie these problems.We have investigated the effect of diabetes on circulating concentrations of regulatory hormones with respect to calbindin-D mRNA concentrations. Three rat groups were studied; control (CP), streptozotocin-induced diabetic (DP), and insulin-treated diabetic (DPI) pregnant rats. Calbindin-D(9K) and calbindin-D(28K) mRNA abundance in placenta and maternal kidney were measured at days 7, 15, 18 and 21 of gestation, together with serum or plasma concentrations of 1,25 dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)), parathyroid hormone (PTH), PTH-related protein (PTHrP), calcitonin, oestradiol and IGF-I. An increase in placental calbindin-D(9K) mRNA abundance between days 18 and 21 in CP and DPI rats was severely blunted in the DP rats. In contrast, renal calbindin-D(28K) mRNA abundance was greater at days 7, 15 and 18 in DP compared with CP rats, as was calbindin-D(9K) at day 18. Calcitonin concentrations showed no differences between the groups, and both PTH and IGF-I were reduced over the first half of gestation, unlike the calbindins. In contrast, the concentrations of PTHrP and 1,25(OH)(2)D(3) were reduced at term in the DP group compared with the other two groups. Plasma oestradiol concentrations were lower in DP than in CP rats at days 7, 15 and 18, and most striking was the absence in DP rats of the peak of oestradiol seen at day 18 in CP rats. Despite the similarity between changes in placental calbindin mRNA and 1,25(OH)(2)D(3), previous work has shown placental calbindin-D(9K) regulation to be vitamin-D-independent. These studies produce suggestive evidence, therefore, that PTHrP and oestradiol may be involved in the altered calbindin-D expression by kidney and placenta in rat diabetic pregnancy.
T. E. Adrian, A. J. Bacarese-Hamilton, H. A. Smith, P. Chohan, K. J. Manolas, and S. R. Bloom
ABSTRACT
Peptide YY (PYY), a thirty-six amino acid intestinal hormonal peptide with a tyrosine residue at each end (hence YY as Y represents tyrosine in the new peptide nomenclature), was found throughout the gastrointestinal tract of the pig. Concentrations were very low in the foregut (antrum, 3·4 ± 0·3 pmol/g; duodenum, 1·1 ± 1·5 pmol/g), higher in the distal small intestine (ileum, 100 ± 13 pmol/g) and very high in the large bowel (descending colon, 270 ± 45 pmol/g).
Peptide YY was found to circulate in plasma and concentrations rose substantially in response to eating (fasting, 138 ± 15 pmol/l; postprandial, 263 ± 21 pmol/l; P<0·001). There was a small but significant portal/arterial gradient in postprandial PYY levels.
More than 90% of the immunoreactive PYY in gut extracts eluted, on gel permeation chromatography, in an identical position to pure PYY standard, but small amounts of higher molecular weight material, possibly precursors, were detected. In contrast, plasma from fasting pigs contained a large proportion (60–70%) of these large molecular forms. These findings suggest that the putative pro-PYY may be cleared more slowly from the circulation than the 36 amino acid hormonal peptide.
The high concentrations of immunoreactive PYY in the circulation of the young pig may reflect a species difference between pig and man or may indicate an important role for PYY in the developing animal.
J. Endocr. (1987) 113, 11–14
