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PubMed1982

Factors regulating the steroid 11-hydroxylation by non-germinating spores of Cunninghamella elegans (Lendner).

In the presence of malate or citrate sporangiospores of C. elegans were able to hydroxylate cortexolone with a rate twofold exceeding that of the control, water suspended spores. Analysis of the intracellular nicotinamide coenzyme pools revealed an increased NADPH:(NADP+ + NADPH) ratio, indicating more effective NADPH-generating systems in malate- or citrate-stimulating spores. Swollen spores remaining in the pregermination state, retained higher cortexolone-hydroxylating activity in the absence of malate and citrate. In these spores degradation of endogenous alanine and glutamic acid was observed. Possible NADPH-generating systems in C. elegans sporangiospores were discussed.

17-Hydroxycorticosteroids↗
PubMed2004

Analysis of 21-deoxycortisol, a marker of congenital adrenal hyperplasia, in blood by atmospheric pressure chemical ionization and electrospray ionization using multiple reaction monitoring.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder mainly caused by 21-hydroxylase deficit (21-OHD). Deletions or mutations of the CYP21 gene induce the impairment of glucocorticoid and mineralcorticoid synthesis. 17-Hydroxyprogesterone (17-OHP) is the hormonal marker in patients, but not in the heterozygous subjects. Excess 17-OHP is hydroxylated into 21-deoxycortisol (21-DF), and therefore 21-DF can be used as a specific marker for diagnosis of heterozygous individuals. We report an analytical method for analysis of 21-DF in blood samples using electrospray (ESI) and atmospheric pressure chemical ionization (APCI), showing that ESI is very sensitive for the analysis of this marker molecule. The multiple reaction monitoring (MRM) approach was used to increase the specificity and the sensitivity of the method.

Adrenal Hyperplasia, Congenital↗
PubMed1990

Common biochemical pathway of dysmorphogenesis in murine embryos: use of the glucocorticoid pathway by phenytoin.

Phenytoin (5,5-diphenylhydantoin), a common anticonvulsant drug, is known to produce anomalies in the craniofacial region of animals and humans. Furthermore, recent evidence suggests that phenytoin disrupts craniofacial and neural tube morphogenesis by inhibiting the arachidonic acid cascade, a pathogenesis already implicated for glucocorticoids and hyperglycemia in the palate. This study tested the hypothesis that phenytoin interferes with the arachidonic acid cascade via the same biochemical pathway demonstrated for glucocorticoids. The proposed pathway was tested at two levels. First, indomethacin, an inhibitor of the enzyme cyclooxygenase, was used in culture to block the correction of phenytoin-induced defects by arachidonic acid. Second, cortexolone, an anti-glucocorticoid that binds at the glucocorticoid receptor binding site, was tested for its ability to prevent phenytoin-induced teratogenicity. Eighty-four percent of the embryos cultured in phenytoin and 93% of those cultured in phenytoin plus arachidonic acid and indomethacin had neural tube and/or craniofacial deformities. In contrast, only 14% of the embryos cultured in phenytoin plus cortexolone were affected. Indomethacin itself produced anomalies in 83% of the exposed embryos. These data are consistent with the hypothesis that the teratogenic action of phenytoin in murine embryo cultures occurs via the glucocorticoid anti-inflammatory pathway. Thus, the glucocorticoid receptor appears to be responsible for mediating phenytoin-induced teratogenicity.

Animals↗
PubMed1993

The effect of angiostatic steroids and beta-cyclodextrin tetradecasulfate on corneal neovascularization in the rat.

Folkman and coworkers have described angiostatic steroids that markedly inhibit neovascularization of the rabbit cornea when given topically with beta-cyclodextrin tetradecasulfate (beta-CD), yet have minimal or no glucocorticoid or mineralocorticoid activity. Our objective was to extend these observations to another species, the rat. We induced neovascularization by cauterizing rat corneas with silver nitrate/potassium nitrate; drugs were applied topically four times per day for 4 days in most experiments. Submicron sized emulsions of lipid-soluble dexamethasone and the angiostatic steroids 17 alpha-hydroxyprogesterone (1 or 10 mg ml-1) and cortexolone (1 or 10 mg ml-1) were prepared by lecithin encapsulation of drug microcrystals. The vehicle for water-soluble hydrocortisone 21-phosphate (HCP) +/- beta-CD (Molecusol; Pharmatec, Inc) was 10% Tween 20 in Tris-buffered 0.9% saline. Angiogenesis was significantly inhibited only by 1 mg ml-1 dexamethasone (-63.2% when compared with controls), 0.5 mg ml-1 HCP + 1 mg ml-1 beta-CD (-33.4%), and 1 mg ml-1 HCP (-40.2%). HCP (0.5 mg ml-1) or beta-CD (1 or 2 mg ml-1) alone had no significant effect on neovascularization; the inhibition by 1.0 mg ml-1 HCP was not potentiated by 2 mg ml-1 beta-CD. We also tested HCP and tetrahydro-S (TH-S) using 1.5% hydroxypropyl methylcellulose vehicle and beta-CD from Takeda Chemical Industries, Ltd., to simulate the procedure of Folkman and coworkers.(ABSTRACT TRUNCATED AT 250 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1994

Plasma levels of gonadal steroids during final oocyte maturation of striped bass, Morone saxatilis L.

Levels of estradiol-17 beta (E2), testosterone (T), 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (DHP), and 17 alpha,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S) were measured by radioimmunoassay (RIA) in blood plasma of striped bass undergoing final oocyte maturation (FOM). Females were captured just prior to, or in the early stages of, FOM and induced to complete maturation and ovulation with injected human chorionic gonadotropin, synthetic salmon gonadotropin-releasing hormone analogue (sGnRHa; [D-Arg6-Pro9 NEt]-sGnRH), sGnRHa plus the dopamine receptor antagonist, domperidone (DOM), or OVAPRIM, a commercial preparation of sGnRHa + DOM. Their plasma levels of immunoreactive DHP and 20 beta-S were significantly greater at ovulation relative to the time of hormone injection, whereas the plasma levels of E2 and T were greatest at injection and decreased by ovulation and 24 hr thereafter. Plasma levels of 20 beta-S, but not DHP, were sustained at high levels after ovulation. Fish injected only with DOM did not undergo FOM, its associated changes in plasma steroid levels, or ovulation. In females captured at various natural stages of FOM, plasma levels of 20 beta-S and DHP were low during germinal vesicle migration (GVM), peaked coincident with germinal vesicle breakdown, and then decreased near the time of ovulation. Plasma levels of E2 and T were greatest during GVM and decreased as DHP and 20 beta-S levels increased. Analyses of conjugated versus free plasma steroids showed 64-79% of the various hormones to be in the free fraction. RIA of plasma fractionated by reversed-phase HPLC showed that half of the 20 beta-S immunoreactivity coeluted with 5 beta-pregnan-3 alpha,17,20 beta,21-tetrol, a putative 20 beta-S metabolite with 99.7% cross-reactivity in the 20 beta-S RIA. These results indicate that striped bass follow the typical profile of changing plasma steroid levels seen in other teleosts during FOM, with a clear shift from C18 and C19 steroids to C21 steroids. They suggest that both DHP and 20 beta-S, both potent inducers of striped bass FOM in vitro, may play a role in regulating FOM in this species.

Animals↗
PubMed1997

In vitro synthesis of 17,20 beta,21-trihydroxy-4-pregnen-3-one by ovaries of turbot (Scophthalmus maximus L.) during oocyte maturation.

Ovaries from female turbot (Scophthalmus maximus L.), a serial spawner, were incubated in vitro with 17-hydroxy[1,2,6,7-3H]progesterone or [7-3H(N)]pregnenolone (P5-3H) during the spawning season. Several metabolites comigrated on TLC and HPLC with known reference steroids and were identified after chemical reaction and crystallization. Incubation with P5-3H generated many 4-ene steroids, accounting for 55% of total radioactivity, indicating strong 3 beta-HSD activity. The major steroids produced by ovaries were testosterone, androstenedione, and 17,21-dihydroxy-4-pregnene-3,20-dione. In addition, 17,20 alpha-dihydroxy-4-pregnen-3-one was also identified, while small quantities of 17,20 beta,21-trihydroxy-4-pregnen-3-one (20 beta-S) (maximum 1.7% of the total radioactivity) were also synthesized. The identity of 20 beta-S was confirmed in incubates with nonlabeled 17-hydroxyprogesterone by mass spectrometry. Production of 17,20 beta-dihydroxy-4-pregnen-3-one was not apparent.

17-alpha-Hydroxyprogesterone↗
PubMed1998

Endocrine profiles of female striped bass (Morone saxatilis) in captivity, during postvitellogenesis and induction of final oocyte maturation via controlled-release GnRHa-delivery systems.

Plasma levels of reproductive and thyroid hormones were measured in captive striped bass females during postvitellogenesis and the spawning period (March-June). Circulating gonadotropin II (GtH II), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta, 21-trihydroxy-4-pregnen-3-one (17,20beta,21-P) remained low and unchanged in nonmaturing females, while 17beta-estradiol (E2) and testosterone (T) declined throughout postvitellogenesis. Plasma thyroxine (T4) declined significantly in mid-April, while triiodothyronine (T3) increased in mid-May. The only female that ovulated spontaneously had markedly different E2, T, and T3 profiles during postvitellogenesis, and had a surge in plasma GtH II during final oocyte maturation (FOM). The lack of a GtH II surge is presumably responsible for the absence of FOM, but earlier, and as of yet unknown, endocrine disruptions during postvitellogenesis may determine the female's ability to undergo FOM. Treatment of females with a gonadotropin-releasing hormone agonist (GnRHa)-delivery system induced FOM and ovulation within 3 and 10 days, respectively, and resulted in the production of fertile eggs. Plasma GtH II increased continually after GnRHa implantation, even in the presence of declining GnRHa plasma levels. Plasma E2 increased first and peaked prior to FOM, whereas T peaked at the peripheral germinal vesicle (GV) stage. Plasma 17,20beta-P and 17,20beta,21-P increased dramatically at the GV breakdown (GVBD) stage. Plasma T4 was unaffected by the GnRHa treatment, whereas T3 decreased after GnRHa implantation and remained low throughout FOM. Based on the observed hormonal profiles, FOM can be separated into an early phase (lipid-droplet coalescence, GV migration) associated with E2 and T elevations, and a late phase (yolk-globule coalescence, GVBD) associated with 17,20beta-P and 17,20beta,21-P elevation.

Animals↗
PubMed1998

Gonadotrophin-releasing hormone agonist stimulates milt fluidity and plasma concentrations of 17,20beta-dihydroxylated and 5beta-reduced, 3alpha-hydroxylated C21 steroids in male plaice (Pleuronectes platessa).

Spermiating male plaice were caught in the North Sea and acclimatised to laboratory conditions. In two experiments, males were injected intramuscularly with either microspheres or pellets containing gonadotrophin-releasing hormone agonist (GnRHa). Blood was sampled at 2- to 5-day intervals. Individual blood plasma specimens were assayed for testosterone, 5beta-reduced, 3alpha-hydroxy ("5beta,3alpha") steroids and sulphated 17, 20beta-dihydroxy ("17,20beta") steroids. Pooled plasma samples were also assayed for free and sulphated 17, 20beta-dihydroxy-4-pregnen-3-one, free 11-ketotestosterone, and glucuronidated testosterone and 11-ketotestosterone. Plasma concentrations of all steroids were significantly elevated by GnRHa from 2 to 5 days onwards following treatment. The most marked changes occurred in the concentrations of the sulphated 17,20beta steroids, which comprised approximately equal amounts of 5beta-pregnane-3alpha,17,20beta-triol 20-sulphate (3alpha,17, 20beta-P-5beta-S) and 5beta-pregnane-3beta,17,20beta-triol 20-sulphate, rising from ca. 1 to 30-80 ng/ml in the first and from ca. 8 to 80 ng/ml in the second experiment. Concentrations of 5beta, 3alpha steroids matched those of 17,20beta steroids in one experiment. However, in the other experiment, the two RIAs yielded highly disparate results in about 50% of the fish (including males in the control group). The plasma of these fish contained excessive amounts of 5beta,3alpha-immunoreactive material between 10 and 25 days. This material was identified as 3alpha,17, 21-trihydroxy-5beta-pregnan-20-one 21-sulphate (a metabolite of 11-deoxycortisol). All previous studies have indicated that when plasma concentrations of this steroid are high, so are those of 3alpha,17,20beta-P-5beta-S. This is the first indication that these steroids are regulated independently. In a third experiment, milt fluidity and production were assessed at 10, 15, and 25 days following GnRHa implantation. Milt volume and fluidity were significantly enhanced by the GnRHa treatment.

Animals↗
PubMed1999

Induction of ovulation of mature oocytes by the maturation-inducing steroid 17,20beta,21-trihydroxy-4-pregnen-3-one in the spotted seatrout.

Incubation of mature, hydrated, follicle-enclosed oocytes of the spotted seatrout, Cynoscion nebulosus, with the maturation-inducing steroid (MIS), 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S), for 9-12 h resulted in the appearance of ovulated oocytes in the culture media. The ovulation response was concentration-dependent and steroid-specific. The other teleost MIS, 17, 20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), was also a potent inducer of ovulation, whereas progesterone and 11-deoxycorticosterone did not stimulate ovulation above control levels and partially antagonized the action of 20beta-S. The agonist and antagonist activities of these steroids on ovulation are consistent with their relative binding affinities for the ovarian nuclear progestogen receptor previously characterized in this species. Both the RNA synthesis inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide blocked MIS-induced ovulation. This suggests that induction of ovulation by the MIS is through a genomic mechanism of action, and potentially involves the previously characterized nuclear progestogen receptor. Gonadotropin (hCG)-induced ovulation was blocked by addition of the steroid synthesis inhibitor cyanoketone, which was overcome by the addition of 20beta-S, but not pregnenolone. Thus, the most likely mechanism of gonadotropin-induced ovulation is an increase in the synthesis of the MIS. It is concluded that the processes of final oocyte maturation and ovulation are both regulated by the MIS. Whereas final oocyte maturation is mediated by the 20beta-S membrane receptor (P. Thomas and S. Das, 1997, Biol. Reprod. 57, 999-1007), ovulation is regulated by a genomic mechanism and is potentially mediated by the previously characterized nuclear progestogen receptor.

Animals↗
PubMed2001

Plasma steroids in mature common dentex (Dentex dentex) stimulated with a gonadotropin-releasing hormone agonist.

The aim of this study was to identify the major C21 steroids produced in vivo during artificially induced final oocyte maturation and spawning in female common dentex (Dentex dentex). During the spawning season, mature females were treated with a gonadotropin-releasing hormone agonist (GnRHa)-loaded delivery system, with or without pimozide (given as a single dose at the beginning of the experiment). Blood samples were collected at various intervals during the experiment and were assayed for GnRHa, 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta,21-trihydroxy-4-pregnen-3-one (17,20beta,21-P). A higher percentage of ovulated females was observed in GnRHa-implanted fish, which produced over 10 times more eggs than controls. Relative fecundity was highest in the GnRHa + pimozide group and lowest in controls. The viability of naturally released eggs was low (2 to 15%) in all groups. Plasma concentrations of 17,20beta-P in GnRHa-implanted fish did not increase, but those in control fish decreased, such that there was a significant difference between control and treated fish between 2 and 10 days after treatment. In another experiment, ovulating common dentex were injected intramuscularly with a single dose of 50 microg kg(-1) of GnRHa in saline and were sampled for blood at 0, 3, 6, 12, and 24 h postinjection. A single water sample was taken from the tanks at 9 h postinjection, the tanks having been emptied and refilled at 6 h. Measurements were made of plasma and water concentrations of free and conjugated 17,20beta-P, 17,20beta,21-P, 17beta-oestradiol (E2), and GnRHa (plasma only). The GnRHa injection increased plasma levels of all steroids, with free 17,20beta-P reaching maximal levels within 3 h. GnRHa treatment also increased the amounts of free and conjugated steroids released into the water between 6 and 9 h.

Animals↗
PubMed2001

Steroid profiles in cultured female jundiá, the Siluridae Rhamdia quelen (Quoy and Gaimard, Pisces Teleostei), during the first reproductive cycle.

The jundiá Rhamdia quelen (Quoy and Gaimard) is a teleost species from the Siluridae family and is an important species for aquaculture in temperate and subtropical climates. Gonad and blood tissue samples were taken from cultured jundiá females between 1998 and 1999. Plasma concentrations of 17beta-estradiol (E(2)), testosterone (T), 11-ketotestosterone (11-KT), 17-hydroxy-4-pregnene-3,20-dione (17-P), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) were measured by radioimmunoassay and potential correlations with the stage of oogenesis and sexual maturation examined. During the experimental period two spawning episodes were observed. Plasma concentrations of E(2) increased progressively during oocyte development, simultaneously with the appearance of yolk vesicles and increasing amounts of deposited yolk. In female jundiá, the T peak occurred in October and was coincident with the peak in gonadosomatic index. Two distinct peaks of progestogens were detected, corresponding to the two spawning episodes, suggesting that one or more of these steroids might act as the "maturational-inducing steroid" in jundiá. Unusually large amounts of 11-KT were also measured in the plasma of mature jundiá females. The identity of 11-KT was confirmed by thin-layer chromatography. Although the profiles of the other steroids are compatible with the roles proposed for the action of these hormones in other teleosts, the role of 11-KT, normally found only in males, is unknown.

Animals↗
PubMed2001

Effects of maturation-inducing hormone on heterologous gap junctional coupling in ovarian follicles of Atlantic croaker.

A previous ultrastructural study of heterologous (granulosa cell-oocyte) gap junction (GJ) contacts in ovarian follicles of Atlantic croaker suggested that these contacts disappear late during the process of resumption of oocyte meiosis. This observation suggested that, unlike scenarios proposed for a number of other species, uncoupling of GJ is not necessary for the onset of meiotic resumption in croaker follicles. However, the functionality of heterologous GJ contacts and the temporal association between maturation-inducing hormone (MIH)-induced changes in heterologous coupling and resumption of oocyte meiosis have not been examined in Atlantic croaker. These questions were addressed with a cell-cell coupling assay that is based on the transfer of a GJ marker, Lucifer Yellow, from oocytes to granulosa cells. Follicle-enclosed oocytes injected with Lucifer Yellow allowed transfer of the dye into the follicle cell layer, thus confirming that there is functional heterologous coupling between the oocyte and the granulosa cells. Dye transfer was observed in vitellogenic, full-grown/maturation-incompetent, and full-grown/maturation-competent follicles. Treatment of maturation-competent follicles with MIH caused a time-dependent decline in the number of follicles transferring dye. However, although GJ uncoupling in some of the follicles was observed before germinal vesicle breakdown (GVBD, index of meiotic resumption), about 50% of the follicles maintained the ability to transfer dye even after GVBD had occurred. Further, a known GJ inhibitor (phorbol 12-myristate 13-acetate) blocked heterologous GJ within a time frame similar to that seen with MIH but without inducing any of the morphological changes (including GVBD) associated with follicular maturation. In conclusion, uncoupling of heterologous GJ seems insufficient and unnecessary for the onset of meiotic resumption in ovarian follicles of Atlantic croaker.

Animals↗
PubMed2000

Sex steroids relative to alternative mating behaviors in the simultaneous hermaphrodite Serranus subligarius (Perciformes: Serranidae).

This study is the first investigation of reproductive endocrinology in a simultaneously hermaphroditic teleost, the belted sandfish (Serranus subligarius). We address two questions: (1) Do steroid hormone levels vary during the spawning season or during the daily spawning cycle of sandfish? (2) Do hormone levels vary relative to an individual's phenotype-size, frequency of spawning and aggressive behaviors, and proportion of testis in the gonad? We analyzed circulating estradiol-17beta (E2), testosterone (T), 11-ketotestosterone (11KT), 17alpha,20beta,21-trihydroxy-4-pregnen-3-one (20betaS), and 17alpha,20beta-dihydroxy-4-pregnen-3-one (DHP) concentrations in a field population. Only E2 levels were significantly higher at the new and full moon, suggesting peak periods of vitellogenesis at these times. Naturally spawning sandfish were sampled every 2 h during the photophase of a 25-h period (12 pm to 1 pm the following day) and gonadosomatic index, degree of oocyte hydration and ovulation, and plasma levels of E2, T, DHP, and 20betaS were analyzed. E2 and T levels did not vary during photophase, suggesting continuous recruitment of oocytes into vitellogenesis. The 20betaS levels peaked around the time of final oocyte maturation. Since frequency of spawning behaviors changes with body size, we captured individuals of various sizes throughout the spawning season and analyzed circulating levels of hormones. 11KT and 20betaS levels increased significantly with body size. In 1992, we quantified frequency of spawning and aggressive behaviors, circulating T and 11KT levels and testicular mass relative to ovotestis mass in focal animals. 11KT levels tended to be positively correlated with frequency of courting male behavior, but were unrelated to the frequency of aggressive behavior or testis mass. Because hormone levels increased with size and frequency of each spawning behavior changes with size, we propose that sex steroids influence growth-related changes in spawning tactics of individuals.

Aggression↗
PubMed1979

Glucocorticoid receptors and actions in rat thymocytes and immunologically stimulated human peripheral lymphocytes.

After reviewing briefly our earlier studies on glucocorticoid receptors and mechanisms in thymus cells, we have outlined results from the following two areas of current interest in our laboratories: the "life-cycle" of glucocorticoid receptors and complexes in thymus cells, and the levels of glucocorticoid receptors and sensitivity in immunologically stimulated human peripheral lymphocytes. Several of our results on energetics and kinetics of hormone binding to glucocorticoid receptors in rat thymus cells seem to require extension of the simplest model of hormone-receptor transformations in intact cells. ATP-depletion experiments suggest the existence of a nonbinding form of the receptor; "chase" experiments suggest reaction of hormone directly with nuclear-bound receptor; experiments on depletion and replenishment of cytoplasmic receptor using cortisol and dexamethasone suggest the existence of at least two subpopulations of nuclear-bound hormone-receptor complex. We have found that mitogen or immunologic stimulation of human peripheral lymphocytes in culture leads within 24 h or so to a striking increase in the number of glucocorticoid receptor sites per cell. We believe this increase may be due to partial synchronization of the cell population in a phase of the cell cycle in which receptor content is high. Contrary to the widely held view that mitogen-stimulated cells become insensitive to glucocorticoids, our experiments show that with respect to inhibition of thymidine and uridine incorporation and glucose uptake, the cells are highly sensitive to dexamethasone at 24, 48, and 72 h after stimulation with concanavalin A.

Animals↗
PubMed1979

Autoradiographic studies of a glucocorticoid agonist and antagonist: localization of 3H-corticosterone and 3H-cortexolone in mouse brain.

The localization in the mouse brain of corticosterone, the natural glucocorticoid in the mouse, and cortexolone, reported to be a glucocorticoid antagonist, was studied by autoradiography 30 min after in vivo administration of the tritiated compounds. After 3H-corticosterone (3HB) injection, radioactivity was preferentially concentrated in cell nuclei of several structures within the limbic system, and in nuclei of certain neurones of the cerebral cortex and medullar oblongata. This nuclear concentration was abolished after injection of 3H-corticosterone with an excess of unlabelled corticosterone. After 3H-cortexolone (3HS) injection, a diffuse radioactivity was observed throughout the brain. However, a higher concentration of grains was present in the ventral nucleus arcuatus and in the infundibulum. When excess unlabelled cortexolone was administered with 3H-cortexolone this preferential accumulation of grains was abolished. The accumulation of 3H-cortexolone in the medial basal hypothalamic region suggests that cortexolone concentrates preferentially in dexamethasone (DM) target regions, and in addition the autoradiographic results show that the cortexolone-receptor complex does not accumulate in the cell nucleus.

17-Hydroxycorticosteroids↗
PubMed1979

Autoradiographic localization of 3H-glucocorticoids and 3H-cortexolone in mouse pituitary.

Autoradiograms of mouse pituitaries were prepared 30 min after injection of 3H-dexamethasone (3HDM), 3H-corticosterone (3HB) and 3H-cortexolone (3HS) either alone or in the presence of competing unlabelled steroids. 3H-dexamethasone accumulated in cell nuclei of both the pars distalis and the pars nervosa but not in those of the pars intermedia. This preferential accumulation (nuclear/cytoplasmic grain density, 4 : 1) was abolished by the concurrent administration of excess dexamethasone. 3H-corticosterone, to a much less marked extent than 3H-dexamethasone, accumulated in cell nuclei of the pars distalis but not in those of the pars intermedia and the pars nervosa. Excess unlabelled corticosterone diminished nuclear grain density in the pars distalis. After 3-h-cortexolone injection, preferential nuclear uptake was not observed. In a second series of experiments, excess dexamethasone (10 x, 100 x), corticosterone (100 x, 300 x) and cortexolone (100 x, 300 x) administered with 3H-dexamethasone were without effect on cytoplasmic grain density but totally abolished preferential nuclear accumulation. Parallel biochemical studies on kidney cytoplasmic preparations from the same animals showed no differences in total cytoplasmic radioactivity between treatments but marked differences in cytoplasmic bound 3H-dexamethasone. The results demonstrate: i) that dexamethasone binds specifically to cell nuclei of the pars distalis and the pars nervosa and that this nuclear concentration is abolished by competing corticosterone and cortexolone as well as dexamethasone; ii) that corticosterone localizes in cell nuclei of the pars distalis but much less markedly than dexamethasone; iii) that cortexolone fullfils the criteria of a glucocorticoid antagonist at the pituitary cell level.

17-Hydroxycorticosteroids↗
PubMed1992

Elimination of by-products in 11 beta-hydroxylation of substance S using Curvularia lunata clones regenerated from NTG-treated protoplasts.

Stable mutants showing improved 11-hydroxylation of Substance S were isolated, following treatment with N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and regeneration of uninucleate protoplasts of the appropriate fungal strains. This procedure was especially suitable for obtaining more directed 11 beta-hydroxylation of Substance S with Curvularia lunata IM 2901. Apart from producing cortisol (11 beta-hydroxy-S), the parent strain formed several by-products that significantly lowered the yield of the desired 11 beta-hydroxyderivative. Isolated mutants of this microorganism carried out directed 11 beta-hydroxylation with only a small amount of one of the by-products, which resulted in a much higher yield of cortisol.

Biotransformation↗