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- Author: M. M. FERGUSON x
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SUMMARY
Sections of ovaries from 30 Swiss white mice were incubated with ten steroid substrates to demonstrate 3β-hydroxysteroid dehydrogenase activity histochemically. The substrates were: (1) 3β-hydroxypregn-5-en-20-one (pregnenolone), (2) 3β,17α-dihydroxypregn-5-en-20-one (17α-hydroxypregnenolone), (3) 3β-hydroxyandrost-5-en-17-one (DHA), (4) 3β,17β-dihydroxyandrost-5-ene (androstenediol), (5) 3β-sulphoxypregn-5-en-20-one (pregnenolone sulphate), (6) 3β-sulphoxy-17α-hydroxypregn-5-en-20-one (17α-hydroxypregnenolone sulphate), (7) 3β-sulphoxyandrost-5-en-17-one (DHA sulphate), (8) 3β-acetoxypregn-5-en-20-one (pregnenolone acetate), (9) 3β-acetoxyandrost-5-en-17-one (DHA acetate), and (10) 3β-acetoxy-17β-hydroxyandrost-5-ene (androstenediol acetate).
Pregnenolone, 17α-hydroxypregnenolone, DHA and androstenediol gave a colour reaction in the corpora lutea, interstitial tissue, theca interna and stroma of all ovaries examined. The granulosa of many follicles, some thought to be atretic, also contained diformazan granules. 17α-Hydroxypregnenolone did not give as intense a reaction as the other free steroids.
No diformazan was deposited with DHA sulphate as substrate. Pregnenolone sulphate and 17α-hydroxypregnenolone sulphate were used by the same tissues as were the free steroids, although they were much less well utilized.
Utilization of 3β-acetoxy derivatives was similar to that of the free steroids.
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SUMMARY
The distribution of dehydrogenases acting on 3α-, Δ5-3β-, 3β-, 11β-, 16β(androgen)-, 16β(oestrogen)-, 17β-, and 20β-hydroxysteroids in the placentae and foetal membranes of the horse, sheep, goat, cat, dog, ferret, rat, rabbit, guinea-pig and man at various stages of pregnancy is described, and some attempt is made to relate their presence in the tissues with their function.
Δ5-3β-Hydroxysteroid dehydrogenase, of particular interest in view of its important function in steroid biosynthesis, was found in the trophoblast of the horse, cat, dog and man, in the thickened maternal endothelium of the ferret placenta, in the trophoblastic giant cells of the rat, and in isolated cells in the uterine lumen of the guinea-pig in early pregnancy. The enzyme was absent from all other sites examined. Correlation is sought between the distribution of this enzyme, the steroid hormone requirements for the maintenance of pregnancy after ovariectomy, and the chemical processes of steroid production by the placentae of the species examined.
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ABSTRACT
Intravenous glucose tolerance tests were performed in eight adult cats before and after a 4-week treatment with thyroxine. The untreated cats had a mean fasting blood glucose concentration of 7·7 ± 0·3 mmol/l and a mean fasting insulin concentration of 88 ± 31 pmol/l which were not significantly different from mean fasting glucose and insulin concentrations after 4 weeks of thyroxine administration (6·9 ± 0·2 mmol/l and 101 ± 28 pmol/l respectively). At 120 min after glucose injection, the glucose concentration in untreated cats returned to baseline concentrations as did the insulin concentration. However, in the hyperthyroid cats both glucose and insulin concentrations were significantly (P < 0·001) higher (13·6 ± 0·8 mmol/l and 245 ± 17 pmol/l respectively) in comparison with the baseline and untreated cats. The t ½ for glucose disappearance was significantly higher in the cats rendered hyperthyroid, and the glucose disposal rate constant (K) was significantly lower in this group. It is concluded that hyperthyroidism in cats leads to impairment of glucose tolerance possibly due to peripheral insulin resistance.
Journal of Endocrinology (1989) 121, 249–251
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Search for other papers by M. W. SMITH in
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SUMMARY
A technique is described by which the unidirectional influx of sodium into toad bladder mucosal cells can be measured over short periods.
The uptake of sodium, which is linear over a 60 s contact period, changes in a non-linear way when the external sodium concentration is varied from 5 to 115mm.
Vasotocin applied to the serosal surface increases significantly the influx of sodium; amiloride applied to the mucosal surface inhibits influx. This is true whether high or low concentrations of sodium are used to bathe the mucosal surface.
The kinetics for the unidirectional influx of sodium provide direct evidence that the passage of sodium into this tissue is by some means other than simple diffusion.
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The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic–pituitary–thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P<0.0001 for all). Serum total thyroxine (TT4), tri-iodothyronine, free T4 (FT4) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT4 fraction (FFT4) was calculated. Serum thyrotropin (TSH) concentrations were measured in nine animals by validating a heterologous canine TSH assay with recombinant feline TSH as a standard. FT4, FFT4, NEFAs, and leptin were significantly higher in obese cats. FT4 had the strongest positive correlation with obesity indices BF, BMI, girth, NEFA, and leptin. Fatty acids oleate and palmitate were shown to inhibit T4 binding to pooled cat serum in vitro, suggesting the possibility that this mechanism was also relevant in vivo. Serum TT4 and TSH did not rise significantly. The implications for thyroid hormone (TH) action are not yet clear, but fatty acids have been proposed to inhibit the cellular uptake of TH and/or pituitary TH receptor binding, leading to TH resistance. Increased leptin may also alter sensitivity to negative feedback of TH. In conclusion, feline obesity is associated with a significant increase in FT4 within the normal range; future investigation into the cellular thyroid status will be necessary to establish cause and effect in this obesity model.
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SUMMARY
The human pronephros showed no hydroxysteroid dehydrogenase activity. The human mesonephros, like piscine and amphibian mesonephroi had 16β- and 17β-hydroxysteroid dehydrogenase activity and a possible function of the human mesonephros is suggested. Metanephric kidneys had 3α-, Δ5-3β-, 3β-, 6β-, 16α-, 16β-, and 17β-hydroxysteroid dehydrogenases; 11β-hydroxysteroid dehydrogenase was present in all adult mammalian metanephric kidneys surveyed. 3α-Hydroxysteroid dehydrogenase was selectively present and very active in the proximal and distal convoluted tubules, particularly of the juxta-medullary glomeruli. This function is thought to be related to the excretion of 3α-ketosteroids. 11β-Hydroxysteroid dehydrogenase was confined to the collecting tubules and its possible involvement in the metabolism of cortisol, aldosterone or androgens in the kidney is noted. 17β-Hydroxysteroid dehydrogenase may be concerned in the excretion of the sex steroids; it occurs throughout the nephron. Δ5-3β-, 16α-, and 16β-hydroxysteroid dehydrogenases were not as active histochemically in the kidney as the 3α-, 3β-, 11β- and 17β-hydroxysteroid dehydrogenases.
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Search for other papers by D. K. MASON in
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SUMMARY
Cortisol utilization by salivary glands, kidneys and adrenals of various mammals has been compared by using a standard histochemical technique for the demonstration of hydroxysteroid dehydrogenases. 11β-Hydroxysteroid dehydrogenase activity was localized in salivary gland ducts, renal collecting and convoluted tubules and in the adrenal cortex of some species. There was no obvious relationship between the levels of enzyme activity in the salivary glands, kidneys and adrenals. Neither was the presence of 11β-hydroxysteroid dehydrogenase in salivary glands particularly associated with mucous or serous secretion, nor were sex differences in levels of activity evident.
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[35S]Methimazole and [35S]propylthiouracil were shown to accumulate in mouse sub-mandibular gland in vivo, with maximal tissue: plasma ratios being achieved at the lowest dose of drug studied (0·1 μg/animal). Autoradiography of submandibular glands showed that the drugs were localized to the intralobular ductal epithelium and within the lumen of the convoluted granular tubule, which was identical to the localization of radiolabelled iodide. Histochemical studies indicated that this was the site of peroxidase activity within the gland. Drug accumulation persisted when iodide trapping was competitively inhibited using perchlorate. These data suggest that antithyroid drug accumulation by this tissue is not dependent on the anion trap; the localization of drug and iodide at the site of peroxidase activity suggest that this may be an important factor in the mechanism of drug accumulation, possibly related to subsequent drug metabolism.
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Radiolabelled [35S]propylthiouracil and [35S]methimazole were shown to accumulate in mouse thyroid gland in vivo, with maximal tissue/plasma ratios and maximal intrathyroidal levels of 35S-labelled drug being seen at the lowest dose of drug studied (0·1 μg/animal). Pretreatment with sodium perchlorate (10 mg) abolished iodide trapping by the thyroid and caused a fall in accumulation of both [35S]methimazole and [35S]propylthiouracil, although this effect was not seen at higher doses of drug, when tissue/plasma ratios approached unity. These data suggest that thiourylene antithyroid drug accumulation by the thyroid gland does not depend directly on the anion trap, and it is suggested that this accumulation might depend on subsequent intrathyroidal drug metabolism.
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SUMMARY
11β-Hydroxysteroid dehydrogenase can be demonstrated histochemically by incubating tissues with nitro blue tetrazolium (2,2′-di-p-nitrophenyl-5,5′-diphenyl-3,3′-(3,3′-dimethoxy-4,4′-diphenylene) ditetrazolium chloride), NAD or NADP and an appropriate steroid. Suitable steroid substrates are: (1) 11β-hydroxyandrost-4-ene-3,17-dione (11β-hydroxyandrostenedione), (2) 3,11β-dihydroxyoestra-1,3,5(10)-trien-17-one (11β-hydroxyoestrone), (3) 3α,11β-dihydroxy-5α-androstan-17-one, (4) 3α,11β-dihydroxy-5β-androstan-17-one and (5) 11β-hydroxypregn-4-ene-3,20-dione(11β-hydroxyprogesterone).
11β-Hydroxysteroid dehydrogenase activity was found in the Leydig cells of six human testes from subjects ranging in age from 12 to 57 yr. with all five substrates.
The Leydig cells of the mouse testis contain demonstrable 11β-hydroxysteroid dehydrogenase activity and the volume of reactive tissue increases regularly between birth and the end of the 10th week of postnatal life; this growth curve is sigmoid in form. An extremely weak histochemical reaction with human placenta obtained at term was observed, 11β-hydroxyandrostenedione being the only substrate utilized to any extent. A specimen of hydatid mole, however, showed intense 11β-hydroxysteroid dehydrogenase activity with all substrates surveyed. 11β-Hydroxysteroid dehydrogenase was also found in the ova, granulosa, theca interna, interstitial tissue and corpora lutea of the mouse ovary.
