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Biomedical subjects

A P Scott

Publications and source records attributed to A P Scott.

At least 19 recordsLinked to original sources
PubMed1992

17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate is a potent odorant in precocious male Atlantic salmon (Salmo salar L.) parr which have been pre-exposed to the urine of ovulated females.

Electrophysiological recordings from the olfactory epithelium have shown that 17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate (17,20 beta-P-sulphate; a conjugate of the oocyte-maturation-inducing steroid in teleosts) is a potent odorant in precocious male Atlantic salmon (Salmo salar L.) parr. However, the olfactory epithelium of these fish only appeared to be responsive to the steroid after stimulation with the urine of ovulated female Atlantic salmon. Immature fish did not respond at any time. Stimulation with urine from immature and precocious male Atlantic salmon parr did not make the olfactory epithelium of precocious male salmon parr responsive to the steroid. 17,20 beta-P-sulphate was found in the urines of ovulated females, precocious male parr and mature male Atlantic salmon. The findings are discussed in relation to the possible role of 17,20 beta-P-sulphate in the physiology of Atlantic salmon.

Animals↗
PubMed1992

In vitro biosynthesis of steroids, including 11-deoxycortisol and 5 alpha-pregnane-3 beta,7 alpha,17,20 beta-tetrol, by ovaries of the goldfish Carassius auratus during the stage of oocyte final maturation.

To examine the production of steroids with potential oocyte maturation-inducing or pheromonal activity in the goldfish (Carassius auratus) we have incubated mature ovaries of this species with 17-[3H]hydroxyprogesterone. The metabolites in the unconjugated, glucuronide, and sulfate fractions were identified by chromatography, microchemical reaction, and, in most cases, crystallization to constant specific activity. A major metabolite, present in all three fractions, was tentatively identified as 5 alpha-pregnane-3 beta,7 alpha,17,20 beta-tetrol. Although 17,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) was found in only low yield (as a sulfate), the presence of the tetrol indicates that it is synthesized in high yield but very rapidly metabolized. The relative proportions of 17,20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P), 11-deoxycortisol (17,21-dihydroxy-4-pregnen-3,20-dione) and 17,20 beta,21-trihydroxy-4-pregnen-3-one (17,20 beta,21-P) varied significantly between incubations and may be affected by the maturational state of the ovary or the method used to stimulate oocyte maturation. Testosterone was present predominantly as its glucuronide. Significant production of glucuronides and sulfates was observed in all incubations. Twenty-five to 30% of the radioactivity remained associated with the tissue, but the distribution of activity between the metabolites did not differ greatly from that found in the medium. These results indicate that 11-deoxycortisol and its 20 beta-reduced derivative (17,20 beta,21-P) may be significant in spawning female goldfish.

17-alpha-Hydroxyprogesterone↗
PubMed1992

17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate: a major new metabolite of the teleost oocyte maturation-inducing steroid.

This paper describes the discovery of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one 20-sulphate (17,20 beta-P-sulphate) in urine of male and female plaice Pleuronectes platessa, in female Atlantic salmon Salmo salar and in female Dover sole Solea solea. 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) induces oocyte final maturation in teleosts and, whereas levels of the free steroid in maturing/ovulating female plaice are generally less than 1 ng ml-1 and poorly associated with the stage of maturation, the levels of 17,20 beta-P-sulphate are around 1500 ng ml-1 urine, 11 ng ml-1 blood plasma and six-fold higher in maturing than in nonmaturing fish. There are also high levels in spermiating male plaice (ca. 2300 ng ml-1 urine and 20 ng ml-1 blood plasma). 17,20 beta-P-sulphate cannot be hydrolysed by snail (Helix pomatia) sulphatase, but can be completely solvolysed by treatment with trifluoroacetic acid (TFA)/ethyl acetate (1/100, v/v) at 45 degrees for 18 hr. A number of other sulphated steroids have been identified in plaice urine: cortisol, 11-deoxycortisol and 3 alpha,17 alpha,21-trihydroxy-5 beta-pregnan-20-one (which can all be hydrolysed by snail juice); 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one and 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (which can both be solvolysed by TFA/ethyl acetate).

Analysis of Variance↗
PubMed1991

Levels of 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one, 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane, and other sex steroids, in blood plasma of male dab, Limanda limanda (marine flatfish) injected with human chorionic gonadotrophin.

In a previous study, plasma sex steroid levels were measured in female dab (Limanda limanda) induced to ovulate by injections of human chorionic gonadotrophin (HCG). In the present study, a similar experiment was carried out on male dabs. In common with female dabs, 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one and 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane showed the greatest response. Their plasma levels increased, respectively, from 6 +/- 1.6 and 13 +/- 6.2 ng/ml to ca. 62 ng/ml within 36 hr and then decreased. Levels of both steroids remained low in fish injected with saline. There was no statistically significant effect of HCG on plasma testosterone or 11-ketotestosterone concentrations. Initial levels of both hormones were between 10 and 20 ng/ml, and decreased simultaneously in both HCG- and saline-injected fish. Levels of 17 alpha-hydroxy-4-pregnen-3,20-dione, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, 11-deoxycortisol, and 17 alpha,20 beta, 21-trihydroxy-4-pregnen-3-one were mostly below the detection limits of the assays (0.4 ng/ml). There was no statistically significant effect of HCG on either the total volume of milt collected or the proportion occupied by spermatozoa.

Animals↗
PubMed1990

Identification of, and development of radioimmunoassays for 17 alpha, 21-dihydroxy-4-pregnene-3,20-dione and 3 alpha,17 alpha, 21-trihydroxy-5 beta-pregnan-20-one in the ovaries of mature plaice (Pleuronectes platessa).

Ovaries from a female plaice (Pleuronectes platessa) that had been injected with human chorionic gonadotrophin were incubated in vitro with 17 alpha-hydroxy[1,2,6,7-3H]progesterone. The major steroids produced by the ovaries were tentatively identified as 17 alpha,21-dihydroxy-4-pregnene-3,20di-one (11-deoxycortisol; 17,21-P), 17 alpha,21-dihydroxy-5 beta-pregnane-3,20-dione (3 alpha, 17,21-P-5 beta). A high proportion of these steroids was found in a conjugated form (sulphates or glucuronides). Radioimmunoassays were developed for 11-deoxycortisol and for 3 alpha,17,21-P-5 beta and were applied to fractions of mature male and female plaice plasmas and plaice ovarian incubates that had been separated on thin-layer chromatography. The presence of all three steroids, in vivo and in vitro, was confirmed. Particularly high amounts of conjugated 3 alpha,17,21-P-5 beta were found in the plasma of mature females (200-400 ng ml-1). The 3 alpha,17,21-P-5 beta radioimmunoassay also identified 3 alpha,17 alpha-dihydroxy-5 beta-pregnane-20-dione in all three fluids, despite the fact that this steroid was not among the radioactive incubation products of the ovary. These findings are compared with those from another flatfish, the dab (Limanda limanda), where the major gonadal steroids have been shown to be 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one and its 5 beta-pregnane (3-keto and 3 beta-hydroxyl) metabolites.

17-Hydroxycorticosteroids↗
PubMed1990

Plasma levels of ovarian steroids, including 17 alpha,21-dihydroxy-4-pregnene-3,20-dione and 3 alpha,17 alpha,21-trihydroxy-5 beta-pregnan-20-one, in female plaice (Pleuronectes platessa) induced to mature with human chorionic gonadotrophin.

In one previous paper we reported on the identification of 11-deoxycortisol and 3 alpha,17 alpha,21-trihydroxy-5 beta-pregnan-20-one in the ovaries and plasma of mature female plaice and also described the development of radioimmunoassays for these two steroids. The present paper describes temporal changes in plasma levels of the free and conjugated forms of these and of some other steroids (17 alpha,20 beta-dihydroxy-4-pregnen-3-one, 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one, 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one, 17 alpha-hydroxy-4-pregnen-3-one, testosterone, and 17 beta-oestradiol) in female plaice injected with and without human chorionic gonadotrophin (HCG). Oocyte final maturation, but not ovulation, was induced by HCG injections. Levels of most of the steroids were also elevated by the HCG injections and were significantly higher than in control fish throughout the experiment (112 hr). The two most abundant steroids were 11-deoxycortisol and 3 alpha,17 alpha,21-trihydroxy-5 beta-pregnan-20-one (up to 600 ng ml-1). Only relatively small amounts of 17 alpha-hydroxy-4-pregnen-3,20-dione (less than 15 ng ml-1), 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, and 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one (less than 5 ng ml-1) were found. 17 alpha,20 beta,21-Trihydroxy-4-pregnen-3-one was not present. Testosterone and 17 beta-oestradiol levels rose briefly, in response to the first of the two HCG injections, and then fell significantly. The ratio of conjugated to free steroids (except for 17 alpha-hydroxy-4-pregnene-3,20-dione and 17 beta-oestradiol) was almost always greater than 1. In the HCG-injected fish, there was a significant negative correlation between the response of 17 beta-oestradiol levels and the response of 11-deoxycortisol and 3 alpha,17 alpha,21-trihydroxy-5 beta-pregnan-20-one levels. This further confirms that, as teleosts approach the time of full maturity, there is switch-over in the ovaries from predominantly C19 and C18 steroid production to predominantly C21 steroid production.

17-Hydroxycorticosteroids↗
PubMed1990

Effects of steroids and human chorionic gonadotrophin on in vitro oocyte final maturation in two marine flatfish: the dab, Limanda limanda, and the plaice, Pleuronectes platessa.

This study investigated the role of gonadotrophin and steroids in the induction of in vitro oocyte maturation in dab (Limanda limanda) and plaice (Pleuronectes platessa), two marine flatfish (Pleuronectiformes) in which the oocytes mature and ovulate in groups (or batches). Clusters of folliculated oocytes were incubated for 3 days with a range of doses of either human chorionic gonadotrophin (HCG) or synthetic steroids with a wide range of structures. They were also incubated with extracts from cultures of HCG-stimulated ovaries. Oocytes were always more responsive to HCG than to steroids, and the median efficient doses obtained with HCG were negatively correlated with oocyte diameters. Bioassay sensitivity to steroids was low when compared with other teleosts, and intraassay variability was high, particularly in plaice. Despite the high variability, a common pattern in specificities to steroids was obtained for the two species, which was also similar to other teleost species. Among the most effective steroids found were 17 alpha,20 beta-dihydroxy-4-pregnen-3-one and 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one. Extracts from incubates were ineffective. The significance of these findings and possible ways to reduce assay variability and improve sensitivity are discussed.

Animals↗
PubMed1990

Plasma levels of ovarian steroids, including 17 alpha-20 alpha-dihydroxy-4-pregnen-3-one and 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane, in female dabs (Limanda limanda)--marine flatfish--induced to mature and ovulate with human chorionic gonadotrophin.

Human chorionic gonadotrophin (HCG) effectively stimulated oocyte final maturation and ovulation in female dabs (Limanda limanda) within 5 days of injection, and this was accompanied by significant changes in blood plasma steroid levels. The steroids which showed the greatest responses to the HCG injections were the ones previously found to be the major products of the ovaries in vitro: 17 alpha-20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P) and 3 beta,17 alpha,20 alpha-trihydroxy-5 beta-pregnane (3 beta,17,20 alpha-P-5 beta). 17,20 alpha-P responded more rapidly with peak levels after 32 hr of injection (115 ng ml-1), but 3 beta,17,20 alpha-P-5 beta reached higher levels ca. 12 hr later (320 ng ml-1). Levels of both steroids were not significantly different from initial values by the time of ovulation. 17 alpha,20 beta-Dihydroxy-4-pregnen-3-one, which is likely to be the oocyte maturation-inducing steroid (MIS) in the dab, showed a significant but very variable rise in levels (between 1 and 10 ng ml-1 in individual fish). 17 alpha-Hydroxy-4-pregnene-3,20-dione levels peaked at 6 ng ml-1 between 30 and 36 hr after HCG injection. Of the other C21 steroids identified in the ovaries of teleosts, 17 alpha,20 beta-21-trihydroxy-4-pregnen-3-one could not be detected, and 17 alpha,21-dihydroxy-4-pregnene-3,20-dione (11-deoxycortisol) showed nonsignificant changes compared to the saline-injected controls. HCG caused a decrease in estradiol-17 beta levels within 24 hr, but levels then rose again to a maximum of 8.2 ng ml-1 at ovulation time, possibly caused by the presence of vitellogenic oocytes in the ovaries. Changes in testosterone levels, however, were not significantly different between HCG- and saline-injected females. The role of HCG-responsive C21 steroids in the dab is discussed.

Animals↗
PubMed1989

A comparison of alprazolam with amitriptyline in the treatment of patients with neurotic or reactive depression. A report of a randomised, double blind study by a General Practitioner Working Party.

104 patients suffering from neurotic or reactive depression were treated with either alprazolam or amitriptyline in randomised, double-blind fashion. Seventeen patients were either lost to follow-up or withdrawn before week 2 (13 due to side effects and 1 because she was feeling better). A further 7 patients did not comply with the protocol, giving a total of 24 patients whose data were not considered suitable for inclusion in the analysis of therapeutic assessments. Evaluation of the 80 patients (40 in each group) who completed at least 2 weeks of the 4-week study demonstrate that both treatments produced a statistically significant response rate. There was a more rapid effect in those patients who received amitriptyline, but there was no significant difference in response between the treatment groups after 4 weeks treatment. Analysis of safety and side effect data on 101 patients (50 treated with alprazolam and 51 with amitriptyline) shows no statistically significant difference in the overall number of side effects experienced in each group, although 11 of those patients who received amitriptyline withdrew because of adverse reactions before completing the study compared to 6 in the alprazolam group. These results suggest that alprazolam may be a useful treatment for patients with neurotic or reactive depression not requiring hospitalisation.

Adult↗
PubMed1989

Synthesis of 20 alpha-hydroxylated steroids by ovaries of the dab (Limanda limanda).

Dab (Limanda limanda) ovarian fragments were incubated in vitro with either [4,7-3H]pregnenolone or 17 alpha-hydroxy[1,2,6,7-3H]progesterone to investigate the pattern of steroidogenesis. A major enzyme found in the dab ovary was 20 alpha-hydroxysteroid dehydrogenase. Among the steroids that were tentatively identified in ovarian incubates were 17 alpha,20 alpha-dihydroxy-4-pregnen-3-one (17,20 alpha-P). 17 alpha,20 alpha-dihydroxy-5 beta-pregnan-3-one, 3 beta, 17 alpha,20 alpha-trihydroxy-5 beta-pregnane (3 beta,17,20 alpha-P-5 beta), and 3 alpha,17 alpha,20 alpha-trihydroxy-5 beta-pregnane. The presence of these steroids in plasma of mature female and male dabs was studied by radioimmunoassay. The antiserum was raised against 17,20 alpha-P. The 17,20 alpha-[3H]P label was produced by incubating place milt with 17 alpha-hydroxy [3H]progesterone. The radioimmunoassay was shown to have a high cross-reaction with the 5 beta-reduced analogues of 17,20 alpha-P and was therefore used, in conjunction with thin-layer chromatography, to measure the steroids. High concentrations of both 17,20 alpha-P and 3 beta,17,20 alpha-P-5 beta found in female and male dab plasma. The possible role of these steroids is discussed.

17-alpha-Hydroxyprogesterone↗
PubMed1989

Seasonal variations in testicular germ cell stages and in plasma concentrations of sex steroids in male rainbow trout (Salmo gairdneri) maturing at 2 years old.

Male rainbow trout of an autumn- and a spring-spawning strain were sampled every 28 days over a period of 2 years, starting when they were approximately 6 months old. Plasma concentrations of testosterone (T), 11-ketotestosterone (11-K), and 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P) were measured by radioimmunoassay. A histometric method was used to determine the absolute quantities of several germ cell stages, including spermatogonia B, spermatocytes, spermatids, spermatozoa, and resorbing spermatozoa. The general pattern of gonadal development in the two strains was similar, e.g., steroids peaking in the order T----11-K----17,20 beta-P. However, there were a large number of differences--in the timing of first appearance of various parameters, in the timing and magnitude of various peaks, in the histological appearance of the regressing testes, and in the heterogeneity of the male population. T and 11-K levels were not associated with any particular germ cell stage in the two strains. Peak 17,20 beta-P levels coincided with the period when ovulated females were present and milt production was maximal.

Animals↗
PubMed1989

Radioimmunoassay investigations of 20 beta-hydroxylated steroids in maturing/ovulating female rainbow trout (Salmo gairdneri).

Radioimmunoassays, combined with thin-layer chromatography, have been used to test for the presence of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, 17 alpha,20 beta,21-trihy-droxy-4-pregnen-3-one, and 20 beta-hydroxy-4-pregnen-3-one, and for the presence of their 5-pregnene and 5 alpha-pregnane analogs, in the blood and ovarian incubation media of maturing/ovulating female rainbow trout (Salmo gairdneri). All of these steroids have previously been shown to be more or less equipotent in in vitro oocyte final maturation assays. Only two steroids were found: 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, the presence of which has already been firmly established, and 17 alpha,20 beta, 21-trihydroxy-4-pregnen-3-one, which has not been previously identified in rainbow trout. The amounts of 17 alpha,20 beta, 21-trihydroxy-4-pregnen-3-one found in vivo and in vitro were, however, only 1-1.5% of those of 17 alpha,20 beta-dihydroxy-4-pregnen-3-one, and therefore seem unlikely to play a significant role in the induction of oocyte final maturation.

17-Hydroxycorticosteroids↗
PubMed1989

Seasonal variations in plasma and pituitary levels of gonadotrophin in males and females of two strains of rainbow trout (Salmo gairdneri).

Male and female rainbow trout of an autumn- and a winter-spawning strain were sampled every 28 days over a period of 2 years, starting when they were approximately 6 months old. Plasma and pituitary levels of gonadotrophin (GTH) were measured by a radioimmunoassay that preferentially detected the gonadotrophin referred to as either GTH II or "maturational and ovulatory" GTH. The general pattern of gonadal development and the profile of GTH in plasma and pituitary were similar in the two strains, except that the timing was different. Gonadal development in both sexes began about 9 months before spawning, concomitant with an increase in pituitary GTH content. In both sexes, pituitary GTH levels rose dramatically by about 50,000-fold, peaking at the beginning of spawning. They remained high many months thereafter, before falling slowly. Plasma GTH levels during the reproductive cycle were different in the two sexes. In both sexes plasma GTH levels remained very low and unchanged until shortly before full sexual maturity was reached. GTH levels then rose only slightly in males, but markedly in females. The slightly elevated GTH levels persisted many months in males, throughout the period when they could be stripped of milt, but in females they were elevated only a short time around ovulation. These results suggest that although a GTH II-like gonadotrophin is present in the pituitary gland throughout the period of gonadal growth, it does not appear to be released in any substantial amounts into the blood until near spawning.

Animals↗
PubMed1989

Conjugates of ovarian steroids, including 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (maturation-inducing steroid), accumulate in the urine of a marine teleost (plaice; Pleuronectes platessa).

Free and conjugated 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20 beta-P), 17 alpha,21-dihydroxy-4-pregnene-3,20-dione (11-deoxycortisol) and 3 alpha,17 alpha,21-trihydroxy-5 beta-pregnan-20-one (3 alpha,17,21-P-5 beta) were measured by radioimmunoassay in matching blood plasma and urine samples from plaice (Pleuronectes platessa) females at several ovarian maturity stages: post-vitellogenesis (IV), final oocyte maturation (V), and ovulation (VI). Free steroids were generally low in all samples. Conjugated steroids were up to 2 orders of magnitude higher in urine than in plasma samples. Conjugated 17,20 beta-P was higher in stage V than in stage IV or VI females. Conjugated 11-deoxycortisol was higher in stage IV and V females. Conjugated 3 alpha,17,21-P-5 beta was higher in stage V and VI females. These results support earlier studies which indicated that 17,20 beta-P was the most likely maturation-inducing steroid (MIS) in plaice, and that the urine might be a vehicle for steroid pheromones synthesized by the gonads.

Animals↗
PubMed1988

Structure-activity relationships of C21 steroids in an in vitro oocyte maturation bioassay in rainbow trout, Salmo gairdneri.

Rainbow trout, Salmo gairdneri, oocytes were used in an in vitro bioassay to test for the potency of C21 steroids in inducing final maturation. A wide range of steroids was used and most of the assays were replicated at least 3 times and up to 10 times with the most effective steroids. 17 alpha,20 beta-Dihydroxy-4-pregnen-3-one (17,20 beta-P), which has been identified as the natural maturation-inducing steroid in Salmoniformes, was used as the reference steroid. Four steroids, 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one; 3 alpha,17 alpha,20 beta-trihydroxy-5 alpha-pregnane; 3 beta,17 alpha,20 beta-trihydroxy-5 alpha-pregnane; and 3 alpha,17 alpha,20 beta,21-tetrahydroxy-5 alpha-pregnane were found to be equipotent with 17,20 beta-P. Analysis of the structure-activity relationships indicated that, for maximum biological activity, steroids must have a planar nucleus (as in delta 4 and 5 alpha-reduced steroids), a hydroxyl or keto group at position 3, and hydroxyl groups at positions 17 and 20 beta. Steroids with delta 5 or 5 beta-reduced conformations and/or hydroxyl or keto groups at position 11 had a much reduced biological activity.

Animals↗