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Search for other papers by MARION B. R. GORE in
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SUMMARY
Dehydrogenation of androsterone, catalysed by both particulate and soluble fractions of rat ventral prostate, has been demonstrated in vitro by spectrophotometric and chromatographic methods. A difference has been observed between dehydrogenases in the particulate and soluble fractions in their acceptance, under uniform experimental conditions, of the 5α and 5β isomers, androsterone and aetiocholanolone, as substrate. The particulate enzyme dehydrogenates androsterone under conditions in which aetiocholanolone is not dehydrogenated, whereas the soluble enzyme utilizes equally androsterone and aetiocholanolone as substrate. An examination of other rat tissues by the chromatographic method has confirmed the widespread occurrence of the soluble dehydrogenase. Particulate dehydrogenase resembling the prostatic enzyme was detected in seminal vesicle and kidney.
Search for other papers by MARION B. R. GORE in
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Search for other papers by D. N. BARON in
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SUMMARY
1. An examination has been made of the free and glucuronide-conjugated corticosteroids in the plasma of normal controls and of patients before and after hypophysectomy. Quantitative measure of the free plasma corticosteroid level 72 hr after withholding cortisone from a hypophysectomized patient (cortisone withdrawal test) is a useful index of completeness of hypophysectomy. Qualitative examination failed to detect corticosteroids in these patients.
2. In all plasmas examined (controls and patients in resting state and after adrenocorticotrophic hormone (ACTH)) the main component of the free corticosteroid fraction is cortisol. In 50% of the plasma samples cortisone was detected. Even after ACTH only occasional traces of corticosterone were detected by the method used in this study.
3. In the glucuronide-conjugated fraction of plasma from subjects in the resting state three compounds, concluded to be tetrahydrocortisol (THF)†, tetrahydrocortisone, and allo-THF†, were regularly seen. After ACTH other material was detected in this fraction which is considered to be tetrahydrocorticosterone (THB), tetrahydro 11-deoxycortisol (THS) and allo-THB. Administration of oral cortisone to hypophysectomized patients did not increase the amounts of THB, THS or allo-THB in the plasma.
Search for other papers by K. J. GURLING in
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Search for other papers by MARION B. R. GORE in
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Search for other papers by D. N. BARON in
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SUMMARY
2-Methyl-9α-fluorohydrocortisone has potent mineralocorticoid and adrenocortical-suppressing activity.
A single oral dose of 0·1 mg lowered the urinary Na/K ratio, causing Na retention and K loss. There was an eosinophilia and a fall in plasma 17-hydroxycorticoids and in urinary 17-oxosteroids and 17-hydroxycorticoids. These effects lasted 24–36 hr, after which time there was a Na diuresis and the values returned to normal.
Doses of 0·3 mg, repeated for 3 days, enhanced these effects, with accompanying oedema and hypokalaemia. No significant effects on carbohydrate or protein metabolism were observed.
The dangers and possible uses of the compound are discussed.
Search for other papers by K. P. McNATTY in
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Search for other papers by MARION GIBB in
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Search for other papers by CAROLYN DOBSON in
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Search for other papers by D. C. THURLEY in
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The aim of the present study was to gain evidence that the level of LH secretion preceding the preovulatory LH surge is an important determinant of follicular maturation and corpus luteum function in the ewe. In addition it was hoped to establish whether the pattern of LH delivery to the ovary (pulsatile v. constant) is a critical factor in the maturation of a preovulatory follicle.
To accomplish this, progesterone-primed anoestrous ewes were repeatedly injected i.v. with LH or luteinizing hormone-releasing hormone (LH-RH), or given an i.v. infusion of LH, over a 72 h period. These animals, together with the appropriate controls, were exposed to a sexually active ram so that oestrous activity could be recorded. All ewes were subjected to intensive blood sampling regimes so that the plasma levels of LH and progesterone could be determined and compared to those which occurred in the same breed of sheep during the oestrous cycle.
Collectively the data suggest that the plasma levels of LH preceding the preovulatory LH surge are an important determinant of follicular maturation as judged by subsequent corpus luteum function. Moreover, they show that follicular maturation can be achieved with widely differing patterns of LH delivery to the ovary during the preovulatory period and that a strict pulsatile delivery of LH may not be an absolute requirement.
Search for other papers by K. J. GURLING in
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Search for other papers by D. N. BARON in
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Search for other papers by MARION B. R. GORE in
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SUMMARY
1. 2-methyl-9α-fluorohydrocortisone was administered orally to two adrenalectomized patients in doses of from 0·025 to 0·1 mg daily.
2. Excessive sodium retention occurred with doses of 0·03–0·1 mg daily, and 0·025 mg sufficed for a positive sodium balance and maintenance of blood pressure.
3. Adrenocortical replacement did not seem to be physiological with this dose in spite of electrolyte control, and there was subjective improvement when cortisone was resumed.
Search for other papers by TS Kostic in
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Search for other papers by SA Andric in
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Search for other papers by D Maric in
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Search for other papers by SS Stojilkovic in
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Search for other papers by R Kovacevic in
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The immobilization stress induces an acute inhibition of testicular steroidogenesis that is mediated by the nitric oxide (NO) signaling pathway. Here we compared the effects of 2-h immobilization stress on in vivo and in vitro rat steroidogenesis at two time points, 0 h and 6 h after the end of the stress session. As expected, serum androgens and human chorionic gonadotropin (hCG)-stimulated progesterone and testosterone production by testicular tissue were inhibited at 0 h, and also at the 6-h time point. Both the acute and sustained inhibitions of in vitro steroidogenesis were accompanied by a significant increase in nitrite, a stable oxidation product of NO. To clarify which subtype of NO synthase (NOS) (constitutive (cNOS) or inducible (iNOS)) participates in down-regulation of testicular steroidogenesis, aminoguanidine hydrochloride (AG), a selective iNOS inhibitor, was employed. Intratesticular injection of AG prevented the sustained, but not the acute, stress-induced decrease in serum testosterone. When added in vitro, it also prevented the sustained decrease in steroid production and increase in nitrite production by testicular tissue, both in a dose-dependent manner and with EC microM. Furthermore, AG added in vivo and in vitro effectively blocked the sustained decrease in 3beta-hydroxysteroid dehydrogenase (3betaHSD) and 17alpha-hydroxylase/C17-20 lyase (P450c17) activities. In all concentrations employed, AG did not affect serum androgens and in vitro steroid and nitrite production in unstressed animals. These results indicate that the NO signaling pathway participates in acute and sustained stress-induced down-regulation of testicular steroidogenesis, presumably through its direct action on 3betaHSD and P450c17. The acute NO production is controlled by cNOS and the sustained production of this messenger is controlled by iNOS.
Search for other papers by Marion Régnier in
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Search for other papers by Matthias Van Hul in
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European Associated Laboratory (EAL) ‘NeuroMicrobiota’, Brussels/Toulouse, Belgium
Search for other papers by Claude Knauf in
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European Associated Laboratory (EAL) ‘NeuroMicrobiota’, Brussels/Toulouse, Belgium
Search for other papers by Patrice D Cani in
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Overweight and obesity are associated with several cardiometabolic risk factors, including insulin resistance, type 2 diabetes, low-grade inflammation and liver diseases. The gut microbiota is a potential contributing factor regulating energy balance. However, although the scientific community acknowledges that the gut microbiota composition and its activity (e.g. production of metabolites and immune-related compounds) are different between healthy subjects and subjects with overweight/obesity, the causality remains insufficiently demonstrated. The development of low-grade inflammation and related metabolic disorders has been connected with metabolic endotoxaemia and increased gut permeability. However, the mechanisms acting on the regulation of the gut barrier and eventually cardiometabolic disorders are not fully elucidated. In this review, we debate several characteristics of the gut microbiota, gut barrier function and metabolic outcomes. We examine the role of specific dietary compounds or nutrients (e.g. prebiotics, probiotics, polyphenols, sweeteners, and a fructose-rich diet) as well as different metabolites produced by the microbiota in host metabolism, and we discuss how they control several endocrine functions and eventually have either beneficial or deleterious effects on host health.
Search for other papers by Marion Régnier in
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Search for other papers by Matthias Van Hul in
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European Associated Laboratory (EAL) ‘NeuroMicrobiota’, Brussels/Toulouse, Belgium
Search for other papers by Claude Knauf in
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European Associated Laboratory (EAL) ‘NeuroMicrobiota’, Brussels/Toulouse, Belgium
Search for other papers by Patrice D Cani in
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Search for other papers by K. P. McNATTY in
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Search for other papers by CAROLYN DOBSON in
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Search for other papers by MARION GIBB in
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The temporal relationships between the levels of LH in peripheral plasma and in follicular fluid of ovarian follicles in anaesthetized sheep were investigated for a 10-h period after a single i.m. injection of LH releasing hormone (LH-RH; 100 μg). The ovarian secretion rates of oestradiol and androstenedione and the levels of these steroids accumulating in different sized follicles at varying time-intervals after the LH-RH injection were also compared.
The data show that the rates at which pituitary LH enters and leaves the intrafollicular fluid-filled spaces are substantially slower than those of peripheral blood. Two hours after LH-RH injection the levels of LH in plasma had increased from 1 to 200 ng/ml, whereas in the follicle the levels remained at approximately 2 ng/ml. Ten hours after the LH-RH injection, the levels of LH in plasma had returned to basal values (∼1·4 ng/ml) but in both small and large follicles the levels of LH (∼20 ng/ml) were comparable to those present in similar sized follicles 4 h earlier.
The data also indicate that more than 90% of the oestradiol produced by a large antral follicle (≥5 mm diameter) probably enters the bloodstream without first accumulating within the follicular antrum. Finally it is concluded that the clearance of the small amount of oestradiol which does accumulate in the follicular antrum is negligible compared with the clearance of this hormone from peripheral plasma.
