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ABSTRACT
While intrasexual competition for mates is generally considered to be an androgen-dependent characteristic of reproductively active males, in the Wilson's phalarope (Phalaropus tricolor) it is the female that acquires the brighter nuptial plumage and aggressively competes for access to the less aggressive males. Despite this pronounced sex-role reversal, circulating sex steroid hormones of breeding phalaropes are similar to those of avian species displaying traditional male–female reproductive roles. To investigate whether these behavioural and morphological steroid-dependent differences may be due to differences in target organ metabolism of circulating androgen, [3H]androstenedione in the presence of an NADPH-generating system was incubated with homogenates of brain, pituitary and skin of male and female Wilson's phalaropes collected from a naturally breeding population. Oestrone, 5α-androstanedione and 5β-androstanedione were measured as endpoints of aromatization, 5α-reduction and 5β-reduction respectively. Aromatase activity in the anterior hypothalamus/preoptic area (AHPOA) and posterior hypothalamus was greater in breeding males with high circulating concentrations of testosterone than in females, and activity in the AHPOA was greater in breeding than in non-breeding males (with low circulating testosterone). Aromatase levels did not differ in septum, archistriatum, hyperstriatum or pituitary. 5α- and 5β-reductase were detected in all neuroendocrine tissues sampled and although there were no significant male–female differences, 5α-reductase was greater in the AHPOA of breeding than of non-breeding males. We infer from this that the behavioural sex-role reversal of phalaropes is unlikely to be accounted for by differences in androgen metabolism in neural targets, although the capacity to form greater quantities of oestrogenic and 5α-reduced metabolites in the AHPOA of breeding males may be linked to the expression of masculine copulatory behaviours. Aromatase activity was not detected in skin containing a sexually dimorphic feather tract; however, 5α- and 5β-reductase activities were significantly higher in females than in males and may account for the brighter nuptial plumage of females. These data suggest that alternate determinants of neural responsiveness such as sex-steroid receptor abundance or neural circuitry may underlie atypical sexual behaviours in phalaropes.
Journal of Endocrinology (1989) 122, 573–581
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The number of epidermal growth factor (EGF) binding sites was determined by competitive binding assays in a series of 46 pituitary macroadenomas. A single concentration of 125I-EGF (1 nM) was used for all experiments. In four cases, a displacement curve was obtained by adding increasing concentrations of cold EGF, and Scatchard analysis showed the presence of two classes of EGF binding sites, with Kd1 = 0.62 +/- 0.23 nM and Kd2 = 53.8 +/- 8.2 nM for the high- and low-affinity binding sites respectively. The distribution of EGF binding sites was studied in 42 cases by a single-point assay, in the presence and in the absence of a 100-fold cold EGF excess. A non-parametric distribution of EGF binding sites was observed (median 10.2 fmol/mg membrane protein, range 0.0-332.0). EGF-receptor positivity, defined as EGF binding > or = 10.0 fmol/mg protein, was observed in 23 samples (54.8%), especially in prolactinomas (76.5%, P < 0.05 vs other tumors taken together) and in gonadotrope adenomas (62.5%). EGF binding was higher in invasive than in non-invasive adenomas (median: 12.8 vs 0.0 fmol/mg membrane protein, P = 0.047), and especially in adenomas invading the sphenoid sinus (median 26.7 fmol/mg membrane protein, P = 0.008 vs other adenomas). EGF binding also tended to increase with the grade of supra/extrasellar extension according to Wilson (P = 0.15). Sex steroid receptors (SSRs) were simultaneously determined in both cytosolic and nuclear fractions of 31 pituitary adenomas. Estrogen and progesterone receptors were determined by an enzyme-linked immunoassay and androgen receptors by a competitive binding assay with [3H]methyltrienolone. No correlation could be found between EGF binding and either the gender and gonadal status of the patients, or the expression of SSRs by the adenomas. We conclude that the EGF family of growth factors may play a role in the evolution of a significant subset of human pituitary adenomas, especially in their invasiveness, and that a high EGF binding capacity may represent an additional marker of aggressiveness for these tumors. Sex steroids do not appear to have a significant role in the regulation of EGF binding in vivo in these tumors.
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We have tested the hypothesis that androstenedione (administered as 21-day, slow-release pellets) is converted to active sex steroids and reduces bone turnover in the ovariectomised rat model. We found that ovariectomy resulted in a minor but significant reduction in plasma concentrations of androstenedione and testosterone and a more significant reduction in oestrone (E1) and oestradiol (E2). This was associated with the expected substantial loss of metaphyseal cancellous bone volume. Androstenedione (1.5-100 mg) pellets increased the plasma concentrations of androstenedione and testosterone above those in the ovariectomised (ovx) rats in a dose-responsive manner, whereas E2 plasma concentrations were increased to a minor but significant degree above those in the ovx animals. Androstenedione reduced loss of cancellous bone volume in a dose-dependent fashion by reducing bone turnover. The 1.5, 5 and 100 mg androstenedione-induced effect on bone turnover was not abrogated by simultaneous treatment with Arimidex, an aromatase inhibitor. This implies that the skeletal-protective effect of androstenedione was not oestrogen-mediated.
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ABSTRACT
The mechanism of action of very high doses of corticosteroids, such as those administered as bolus doses in the treatment of inflammatory and immune diseases or those currently used in rodents to isolate the small proportion of medullary thymocytes considered to be corticoresistant, is still undefined. The possible existence of selective local concentration by some tissues, particularly lymphoid organs, cannot be excluded. Therefore, using C57BL/6 mice, the kinetics of lymphoid tissue and plasma radioactivities after i.p. injection of steroids, either alone or with an excess of non-radioactive cortisol hemisuccinate (up to 10 mg/animal, i.e. 500 mg/kg ) were studied. There was a rapid and dose-dependent retention of [3H]corticosterone and [3H]cortisol in the thymuses of cortisol-treated compared with control animals. The spleen also appeared to be capable of accumulating steroids. However, when the tissue/plasma ratio of [3H]steroid concentration and the change in extracellular space in the presence of an excess of non-radioactive cortisol were taken into consideration, only the thymus was able to concentrate steroids above concentrations in the plasma. Moreover, this effect did not appear to be specific for glucocorticoids, since tracer accumulation was also observed when sex steroids were used as tracers. The cells of the reticuloendothelial system may, in part, be responsible for this phenomenon of steroid concentration in lymphoid organs.
J. Endocr. (1988) 117, 373–378
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ABSTRACT
Hepatic microsomal cytochrome P-450 monooxygenase activities were investigated in rainbow trout during an annual reproductive cycle. The fish were kept in tanks supplied with fresh water at a constant temperature of 10 °C. The daily light and darkness cycle was adjusted to follow the natural photoperiod. Sampling was performed once every month for 1 year. Higher benzo(a)pyrene-hydroxylase (or aryl hydrocarbon hydroxylase; AHH), ethoxycoumarin-O-deethylase (ECOD) and ethylmorphine-N-demethylase (END) activities and cytochrome P-450 content were found during the late stage of sexual development in rainbow trout. When monooxygenase activities were expressed on a per cytochrome P-450 basis, sex-dependent differences were observed only for AHH and ECOD activities. It was thus found that sex-dependent variations of END were closely correlated with the total amount of cytochrome P-450. The results indicate that differences exist in hepatic cytochrome P-450 isoenzyme patterns between the sexes in rainbow trout. The similarity of the annual pattern of plasma levels of oestradiol and testosterone to that of sex-dependent differences in the cytochrome P-450 monooxygenases support the contention that sex steroids play a role in regulating the cytochrome P-450 system.
Journal of Endocrinology (1990) 124, 207–213
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ABSTRACT
Studies were conducted in castrated golden hamsters to assess whether sexual dimorphism and sensitivity to sex steroid hormones in the rodent Harderian gland are mediated by an interaction of androgens with specific intracellular receptors. Physical properties, binding kinetics and stereospecificity of the androgen receptor were analysed using [3H]mibolerone as the radioligand. The presence of [3H]mibolerone–androgen receptor complexes with a sedimentation coefficient of 7–8S was demonstrated in Harderian gland cytosol by a linear sucrose gradient ultracentrifugation technique using a vertical rotor. Kinetic analysis revealed an androgen-binding site with an apparent dissociation constant of 0·3±0·07 (s.d.) nmol/l and a saturation binding capacity of 113±15 fmol/mg protein. Displacement studies indicated that unlabelled mibolerone, methyltrienolone, 5α-dihydrotestosterone and testosterone were efficient competitors for the androgen-binding sites, while progesterone, 17β-oestradiol, dexamethasone, dehydroepiandrosterone, ethiocholanolone and 5α-16-androsten-3-one were not. Experiments in long-term castrated animals revealed that the Harderian gland androgen receptor concentration and sedimentation coefficient remained unmodified. The results of these studies were interpreted as demonstrating the presence of a specific high-affinity intracellular androgen receptor in the male hamster Harderian gland.
J. Endocr. (1987) 112, 3–8
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ABSTRACT
Plasma testosterone-binding globulin (TeBG)-binding capacity was determined by equilibrium dialysis in the lesser mouse lemur (Microcebus murinus), a prosimian which exhibits a clear photoperiod-dependent sexual cycle. Plasma TeBG-binding capacity showed significant seasonal changes which were inversely correlated to those of plasma testosterone concentrations. The capacity of TeBG was at its maximum (1·72 ± 0·4 μmol/l) during the sexual rest period and decreased to 0·98 ±0·24 μmol/l during the breeding season when testosterone concentrations were about 200–280 nmol/l. In addition, when males developed a social hierarchy in groups, the decreased sexual function in non-dominant animals was associated with a higher TeBG-binding capacity. However, although TeBG-binding capacity increased when testosterone concentrations decreased either during sexual rest or under social dominance, a positive correlation was found between TeBG-binding capacity and testosterone levels during the breeding season in males with a normal reproductive cycle, i.e. in both isolated and dominant males. This suggests that factors other than sex steroids are involved in the changes in TeBG-binding capacity occurring under seasonal and social influences.
J. Endocr. (1986) 110, 169–175
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SUMMARY
Young adult goldfish treated for 4 weeks with oestradiol, progesterone, or with a synthetic oestrogen or progestogen were used in a variety of tests designed to characterize olfactory function, using electroneurophysiological methods. The following observations were made:
1. The olfactory bulb appeared to be among the most responsive to hormone among the tested regions of the brain.
2. In oestrogenized goldfish and in fish given higher dosages of progesterone, there was a spontaneous slow pattern in the olfactory bulbar EEG. This slow pattern is changed to a desynchronized fast pattern after section at the midbrain—hindbrain level (cerveau isolé). On the other hand, the spontaneous 'normal' desynchronized pattern of progestogen-treated fish is converted to a synchronized slow pattern after similar brain stem transection.
3. Centrifugal modification of afferent-evoked bulbar electrical responses produced by NaCl infusion into the ipsilateral olfactory sac was augmented by hormones in lower doses in the cerveau isolé preparation. Oestradiol and progesterone in higher doses inhibit the centrifugal influence on bulbar responses while the synthetic progestational steroid continued to augment this control even when given at higher doses.
These results suggest that sex steroids alter olfactory function through their stimulatory or inhibitory actions on the goldfish central nervous system, but the nature of their action depends upon dosage level and the particular steroid.
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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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Maintenance of normal male fertility relies on the process of spermatogenesis which is under complex endocrine control by mechanisms involving gonadotropin and steroid hormones. Although testosterone is the primary sex steroid in males, estrogen is locally produced in the testis and plays a very crucial role in male fertility. This is evident from presence of both the estrogen receptors alpha (ERα) and beta (ERβ) in the testis and their absence, as in the case of knockout mice models, leads to sterility. The present study was undertaken to understand individual roles of the two ERs in spermatogenesis and their direct contribution towards the maintenance of male fertility using receptor-subtype-specific ligands. Administration of ERα and β agonists to adult male rats for 60 days results in a significant decrease in fertility, mainly due to an increase in pre- and post-implantation loss and a concomitant decrease in litter size and sperm counts. Our results indicate that ERα is mainly involved in negative feedback regulation of gonadotropin hormones, whereas both ERs are involved in regulation of prolactin and testosterone production. Histological examinations of the testis reveal that ERβ could be involved in the process of spermiation since many failed spermatids were observed in stages IX–XI following ERβ agonist treatment. Our results indicate that overactivation of estrogen signaling through either of its receptors can have detrimental effects on the fertility parameters and that the two ERs have both overlapping and distinct roles in maintenance of male fertility.