Exogenous Steroid Treatment Research Articles

Androgen Inhibition of Reproductive Neuroendocrine Function in Females and Transgender Males.

Ovarian function is controlled by pituitary secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH), which in turn are governed by gonadotropin releasing hormone (GnRH) secreted from the brain. A fundamental principle of reproductive axis regulation is negative feedback signaling by gonadal sex steroids back to the brain to fine-tune GnRH and gonadotropin secretion. Endogenous negative feedback effects can be mimicked by exogenous steroid treatments, including androgens, in both sexes. Indeed, a growing number of clinical and animal studies indicate that high levels of exogenous androgens, in the typically male physiological range, can inhibit LH secretion in females, as occurs in males. However, the mechanisms by which male-level androgens inhibit GnRH and LH secretion still remain poorly understood, and this knowledge gap is particularly pronounced in transgender men (individuals designated female at birth but identifying as male). Indeed, many transgender men take long-term gender-affirming hormone therapy that mimics male-level testosterone levels. The impact of such gender-affirming testosterone on the reproductive axis, both at the ovarian and neuroendocrine level, is a long-understudied area that still requires further investigation. Importantly, the few concepts of androgen actions in females mostly come from studies of polycystic ovary syndrome, which does not recapitulate a similar androgen milieu or a pathophysiology of inhibited LH secretion as occurs in testosterone-treated transgender men. This review summarizes clinical evidence indicating that exogenous androgens can impair neuroendocrine reproductive function in both female individuals and transgender men and highlights emerging experimental data supporting this in recently developed transgender rodent models.

DIAGNOSIS OF ENDOCRINE DISEASE: Sex steroid action in adolescence: too much, too little; too early, too late.

This review aims to cover the subject of sex steroid action in adolescence. It will include situations with too little sex steroid action, as seen in for example, Turners syndrome and androgen insensitivity issues, too much sex steroid action as seen in adolescent PCOS, CAH and gynecomastia, too late sex steroid action as seen in constitutional delay of growth and puberty and too early sex steroid action as seen in precocious puberty. This review will cover the etiology, the signs and symptoms which the clinician should be attentive to, important differential diagnoses to know and be able to distinguish, long-term health and social consequences of these hormonal disorders and the course of action with regards to medical treatment in the pediatric endocrinological department and for the general practitioner. This review also covers situations with exogenous sex steroid application for therapeutic purposes in the adolescent and young adult. This includes gender-affirming therapy in the transgender child and hormone treatment of tall statured children. It gives some background information of the cause of treatment, the patient's motivation for medicating (or self-medicating), long-term consequences of exogenous sex steroid treatment and clinical outcome of this treatment.

Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment

Background: Adrenal insufficiency can result from impaired functions at all levels of hypothalamic-pituitary-adrenal (HPA) axis. We here studied risk factors associated with adrenal insufficiency in children receiving prolonged exogenous steroid treatment for nephrotic syndrome.Method:We performed low-dose Synacthen tests (LDSTs, 0.5 μg/m2) in children with steroid-sensitive nephrotic syndrome 4–6 weeks after discontinuation of the corticosteroid therapy. We measured early morning serum cortisol levels at baseline and at intervals of 10, 20, 30, and 60 min following the stimulation test. We defined normal HPA axis stimulation responses as those with peak cortisol cut-off values >550 nmol/L.Result:We enrolled 37 children for this study research. All children enrolled had normal early morning cortisol levels. However, 13 (35.1%) demonstrated HPA axis suppression (by LDST) 4–+6 weeks after discontinuation of oral prednisolone. Nephrotic syndrome diagnosed before 5 years of age (OR, 0.75; 95% CI, 0.57–0.99; p = 0.043), and steroid-dependence [OR, 5.58; 95% confidence interval (CI), 1.06–29.34; p = 0.042] were associated with increased risk of developing adrenal suppression after steroid discontinuation.Conclusion:HPA axis suppression, may go unnoticed without proper screening. A normal early morning cortisol level (275–555 nmol/L) does not exclude adrenal insufficiency in children with steroid-sensitive nephrotic syndrome. Further screening with LDSTs, particularly in children younger than 5 years at diagnosis, may be warranted.

Comprehensive steroid profiling by liquid chromatography coupled to high resolution mass spectrometry

A steroidomics workflow has been developed in the objective of monitoring a wide range (n >150) of steroids in urine. The proposed workflow relies on the optimization of an adequate SPE extraction step followed by an UHPLC-HRMS/MS simultaneous analysis of both free and conjugated forms of C18, C19 and C21 steroid hormones. On the basis of 44 selected steroids, representative of main classes of steroids constituting the steroidome, the performances of the developed workflow were evaluated in terms of selectivity, repeatability (< 13%) and linearity (R2> 0.985 in the concentration range [0.01–10 ng/mL]). As metabolites identification and characterization constitute the bottleneck of such profiling approaches, a homemade database was created encompassing a large number of characterized free and conjugated steroids (n> 150) for putative steroid-like biomarkers identification purposes. The efficiency of the workflow in highlighting fine modifications within the urinary steroidome was assessed in the frame of an anabolic treatment involving an intra-muscular administration of boldenone undecylenate (2 mg/kg) to veals (n=6) and the investigation of potential steroid biomarkers. Besides monitoring known phase II metabolites of boldenone in the bovine specie, namely, boldenone glucuronide and sulfate, the applied strategy also permitted to observe, upon boldenone administration, a modified profile of epiboldenone glucuronide. Furthermore, 31 signals corresponding to non-identified steroid species could also be highlighted as impacted upon the exogenous steroid treatment. This study is the first to simultaneously investigate both free and conjugated C18, C19 and C21 steroid hormones in their native form using UHPLC-HRMS/MS and allowing their comprehensive profiling. This strategy was probed in-vivo.

A Transgenic Medaka Line with Visible Markers for Genotypic and Phenotypic Sex

Accurate genotyping of sex is required for correct interpretation in any in vivo assays with endocrine disrupting chemicals (EDCs). Visible markers for genotypic sex, if reliable, simplify assays because time-consuming PCR-based genotyping can be skipped. Here, we describe a line of Japanese medaka with a brain-expressed green fluorescent protein (GFP) transgene inserted near the sex-determining locus. When used with a white pigment cell marker, genotypic sex can be determined reliably as early as 3 days after fertilization (well before gonadal sex differentiation). No recombinants were found in more than 2000 progenies. We also introduced a strong ovarian GFP marker into the line with these genetic sex markers, so that phenotypic sex can also be determined reliably at 8 days after hatching. Well-known sex reversal protocols using exogenous steroid treatments of embryos were monitored by this transgenic line, demonstrating the line to be a useful tool for in vivo studies utilizing gonadal sex differentiation of the medaka, especially for screenings of potential estrogenic and androgenic EDCs.

Characterization of gonadal transcriptomes from Nile tilapia (Oreochromis niloticus) reveals differentially expressed genes.

Four pairs of XX and XY gonads from Nile tilapia were sequenced at four developmental stages, 5, 30, 90, and 180 days after hatching (dah) using Illumina HiseqTM technology. This produced 28 Gb sequences, which were mapped to 21,334 genes. Of these, 259 genes were found to be specifically expressed in XY gonads, and 69 were found to be specific to XX gonads. Totally, 187 XX- and 1,358 XY-enhanced genes were identified, and 2,978 genes were found to be co-expressed in XX and XY gonads. Almost all steroidogenic enzymes, including cyp19a1a, were up-regulated in XX gonads at 5 dah; but in XY gonads these enzymes, including cyp11b2, were significantly up-regulated at 90 dah, indicating that, at a time critical to sex determination, the XX fish produced estrogen and the XY fish did not produce androgens. The most pronounced expression of steroidogenic enzyme genes was observed at 30 and 90 dah for XX and XY gonads, corresponding to the initiation of germ cell meiosis in the female and male gonads, respectively. Both estrogen and androgen receptors were found to be expressed in XX gonads, but only estrogen receptors were expressed in XY gonads at 5 dah. This could explain why exogenous steroid treatment induced XX and XY sex reversal. The XX-enhanced expression of cyp19a1a and cyp19a1b at all stages suggests an important role for estrogen in female sex determination and maintenance of phenotypic sex. This work is the largest collection of gonadal transcriptome data in tilapia and lays the foundation for future studies into the molecular mechanisms of sex determination and maintenance of phenotypic sex in non-model teleosts.

The effect of exogenous anabolic steroids on growth performance, testicular and seminal characteristics of yearling Boer goat bucks

The effect of anabolic steroid treatment on young Boer goat bucks (12 months of age; mean body weight of 47.0±3.8kg) was investigated. Bucks were individually housed and randomly allocated to two treatment groups and fed a pelleted maintenance diet (8.5MJME/kg and 13% CP). Bucks in the first group (n=9) received a weekly i.m. injection of 25mg Deca-durabolin (testosterone) for a total period of 16 weeks. The remaining bucks (n=10) served as the controls. At the end of the 16-week treatment phase an additional 12 week recovery monitoring phase (no treatment) was implemented. During the trial semen was collected (artificial vagina) weekly, where semen volume, colour, pH and sperm density and motility was recorded. The body parameters recorded weekly included body weight, scrotal circumference and volume. The body parameters found to be significantly (P<0.05) affected by treatment with the anabolic steroid, was scrotal circumference and volume. This degeneration of the scrotal measurements was ascribed to the negative feedback system induced by the exogenous anabolic steroid treatment (androgenic effect). By the end of the recovery period, the difference in scrotal circumference and volume between the treatment groups had decreased to 7% – with the treated bucks still recording a significantly (P<0.05) lower scrotal volume, compared to the control group (584.4±87.3ml vs 640.0±81.0ml respectively). Despite this reduction in scrotal circumference and volume none of the seminal parameters recorded in the trial (i.e. sperm motility, semen volume and pH, sperm concentration and percentage live sperm) were significantly affected by the steroid treatment. It would also seem as if the inhibitory effect of steroid treatment on testicular development was only temporary and that young males can recover, without any apparent loss in fertility, as measured by semen quality. The lack in body weight response could possibly be ascribed to the age of the animals and the relatively low energy content of the diet.

Addison's disease masked by long term exogenous steroid treatment for presumed polymyalgia rheumatica

Addison9s disease can present insidiously. A 78-year-old woman presented with non-specific symptoms and hyponatremia, with a previous history of polymyalgia rheumatica treated with glucocorticoids. Subsequent investigations were consistent with primary rather than secondary adrenal failure. Primary autoimmune Addison9s disease can present with protean symptoms and diagnosis is often delayed. A high index of suspicion remains the cornerstone of diagnosis.

Relationship between serum gonadotropins and pituitary immunoreactive gonadotropins and steroid receptors during the first FSH increase of the estrous cycle and following steroid treatment in heifers

The objectives were to determine the effects of (i) time during the first FSH increase of the estrous cycle (time-course study) and (ii) exogenous steroid treatment (steroid feedback study) on the relationship between circulating serum gonadotropins, and the proportions of pituitary cells immunoreactive for gonadotropins and steroid receptors during the estrous cycle in heifers. Pituitaries were collected from heifers ( n = 40) slaughtered at 13 h ( n = 8), 30 h ( n = 24) and 66 h ( n = 8) after estrous onset, corresponding to before, during and after the first FSH increase of the estrous cycle. Heifers slaughtered during the FSH increase (at 30 h) either received no treatment ( n = 8), or were treated ( n = 16) with estradiol benzoate and/or progesterone before slaughter. During the time-course study, the proportion of pituitary cells immunoreactive for FSH increased ( P < 0.05) during the first transient FSH increase reflecting serum concentrations. The proportion of pituitary cells immunoreactive for LH was unaltered, a reflection of serum LH concentrations. The proportion of estrogen receptors (ER)-α, but not ER-β, was decreased ( P < 0.05) at 30 h compared with at either 13 or 66 h. During the steroid feedback study, exogenous progesterone with or without estradiol suppressed ( P < 0.05) the proportions of pituitary cells immunoreactive for gonadotropins, serum FSH concentrations and LH pulse frequency. Steroid treatment did not alter the proportion of pituitary cells positive for estrogen receptors (α and β). While progesterone receptors (PR) were not detected in the anterior pituitary by immunohistochemistry during the early estrous cycle or in response to steroid treatment, quantitative real-time PCR revealed that mRNA for progesterone receptors was expressed at very low levels. The expression of pituitary PR mRNA was decreased ( P < 0.05) at 30 and 66 h compared with 13 h, and was suppressed ( P < 0.05) following steroid treatments. Alterations in pituitary steroid receptors are implicated in the differential regulation of gonadotropin secretion during the first transient FSH rise, but not in response to exogenous steroids. The time-course study and steroid feedback responses support the hypothesis that LH pulse frequency is tightly linked to regulation of GnRH pulse frequency. Serum FSH is regulated by its own synthesis, as reflected by pituitary FSH content and perhaps by alterations in pituitary sensitivity to circulating steroids by changes in steroid receptor content.

TINU-associated retinal pigment epithelium detachments: a possible novel posterior segment feature

To report a case of tubulointerstitial nephritis and uveitis syndrome (TINU) with novel posterior segment features of bilateral vitritis and retinal pigment epithelial detachments. This is an interventional case report with fundus photographs and fluorescein angiograms of a 9-year-old girl presenting with bilateral acute anterior uveitis 4 months after a diagnosis of acute tubulointerstitial nephritis. Visual acuities remained normal throughout the 6-month period of follow-up. The anterior and posterior uveitis settled, although retinal pigment epithelial detachments persisted and may be related to the underlying disease process in TINU or exogenous steroid treatment, or both. The idiopathic inflammatory response seen in TINU is traditionally associated with an anterior uveitis. This case demonstrates that there may be more extensive ocular involvement and that posterior uveitis and retinal pigment epithelial detachments may represent emerging features of atypical cases of TINU.

Does exogenous progesterone and oestradiol treatment from the mid-luteal phase induce follicular cysts in goats?

The purpose of the present study was to investigate the effects of exogenous ovarian steroid treatment, which is known to induce follicular cyst experimentally in cows, on ovarian activity in goats. Eleven female Shiba goats with the length of the normal oestrous cycle (approximately 21 days) received subcutaneously either 1 ml of ethanol (control group, n = 4) or 4 mg of progesterone and 2 mg of oestradiol (treatment group, n = 7) daily for 7 days beginning on day 14 of the oestrous cycle (day 0 = ovulation). Ultrasonographic images of the ovary and blood samples were collected daily to monitor the ovarian activity. Ovulation was observed before 1 day after the end of treatment in the control group. In the treatment group, no detectable structures of follicles or corpus luteum (static ovarian condition) were found for 6.0 ± 1.4 days (mean ± S.D.) after the end of treatment. Then, detectable follicles appeared and ovulation was observed in all animals of the treatment group. There was no significant difference in the maximum diameter of the ovulatory follicle between the control and treatment group (4.7 ± 0.4 mm versus 5.1 ± 0.7 mm). The large non-ovulatory follicles, which grew more than 10 mm in diameter were observed after the static ovarian condition in one goat of the treatment group, whereas no turnover of the cystic follicular structures was found. The length of the inter-ovulatory intervals in the treatment group was significantly longer than that in the control group (38.4 ± 7.4 days versus 20.3 ± 0.5 days, P < 0.05). The present results demonstrated that the exogenous treatment of progesterone and oestradiol, which was adapted from the follicular cyst model in cows, did not induce follicular cysts in goats, suggesting that there is/are different mechanism(s) mediating the occurrence of follicular cysts between cows and goats.

Alterations in follicular IGFBP mRNA expression and follicular fluid IGFBP concentrations during the first follicle wave in beef heifers

The objective was to determine the pattern of IGFBP-2, -3 and -4 gene expression and follicular fluid concentrations of IGFBP-2, -3, -4 and -5 during emergence, selection and dominance of the first follicle wave of the estrous cycle in cattle and during exogenous steroid treatment. Heifers ( n = 35) were ovariectomized at 36 ( n = 7), 66 ( n = 8), 84 ( n = 12) and 108 ( n = 8) h after the onset of estrus. Heifers in the 84 h ovariectomy group were sub-divided to receive either no treatment ( n = 6) or were treated with a progesterone-releasing intravaginal device ( n = 6, PRID) and 0.75 mg estradiol benzoate i.m. at the approximate time of ovulation, 30 h post estrus until ovariectomy. Within heifers the four largest follicles recovered following ovariectomy were ranked on size (F1, F2, F3 and F4). At 36 h IGFBP gene expression and follicular fluid IGFBP concentrations were similar in all follicles (F1–F4). Mean diameter of the F1 follicle increased ( P < 0.05) between 36 and 84 h with no difference between 84 and 108 h. The F1 follicle had the highest ( P < 0.05) concentration of estradiol compared with the F2, F3 and F4 at 84 and 108 h. There was no granulosa cell IGFBP-2 mRNA in F1 follicles at 84 or 108 h. Intrafolliclar IGFBP-2 concentrations were lower ( P < 0.05) in the F1 compared with F3 and F4 follicles at 108 h. There was no difference in theca cell IGFBP-4 mRNA expression at 108 h, but amounts of follicular fluid IGFBP-4 were lower ( P < 0.05) in F1 follicles compared with F3 and F4 follicles at 108 h. IGFBP-3 mRNA was localized in the theca layer of all follicles examined with no difference in expression or follicular fluid concentrations during emergence, selection and dominance of the first follicle wave. IGFBP-5 concentrations were higher ( P < 0.05) in follicular fluid of F3 follicles at 108 h compared with the F3 at 36 h. In conclusion follicular dominance was associated with low or decreased follicular fluid concentrations of IGFBP-4 and -5, increased estradiol and differential regulation of IGFBP production.

Brain estradiol content in newborn rats: sex differences, regional heterogeneity, and possible de novo synthesis by the female telencephalon.

Accurate assessment of gonadal steroid levels in the developing brain is critical for understanding naturally occurring steroid-mediated sexual differentiation as well as determining the physiological relevance of exogenous steroid treatments commonly used in the study of this phenomenon. Using RIA, we measured the estradiol (E(2)) content of six regions of the developing brain immediately post partum, 1 d post partum, and after injection of exogenous estradiol benzoate, testosterone propionate, or the aromatase inhibitor formestane. We found sexually dimorphic E(2) content in several regions of the newborn brain. At 2 h of life, there was significantly higher E(2) content in males vs. females in the frontal cortex, hypothalamus and preoptic area but not in the hippocampus, brainstem, or cerebellum. Surprisingly, the female hippocampus had significantly higher E(2) content than all other female regions examined. By d 1 post partum, E(2) levels had decreased precipitously in most brain regions, and only the hypothalamus maintained a sex difference. Injection of female pups with estradiol benzoate raised tissue levels to that of the male in the hypothalamus but 2- to 3-fold higher in the other five regions. Testosterone administration increased E(2) content exclusively in the preoptic area, suggesting local variation in aromatase activity and/or substrate availability. Central administration of formestane decreased estrogen content in the male cortex, hypothalamus, and preoptic area. Formestane treatment also decreased endogenous E(2) in female cortex and hippocampus, suggesting de novo synthesis selectively in these brain regions. These data corroborate and extend previous findings of sex differences in brain E(2) levels perinatally and reveal an unexpected regional heterogeneity in E(2) synthesis and/or metabolism.

Variations of mt1 melatonin receptor density in the rat uterus during decidualization, the estrous cycle and in response to exogenous steroid treatment.

The expression of mt1 receptor protein in the rat uterus was investigated using an anti-mt1 polyclonal antibody against the rat mt1 receptor. A melatonin receptor protein of 37 kDa was detectable by Western blotting in the rat uterine membrane preparations. Autoradiography with the melatonin ligand, 2-[125I]iodomelatonin, was used to localize melatonin receptors in the uterus of the estrous rats and to study the changes of melatonin receptors in pregnancy. Melatonin receptors were found to be localized in the estrous rat uterine antimesometrial stroma. As decidualization of the uterine stroma progressed during pregnancy, the melatonin binding sites were progressively reduced and became confined to the antimesometrial non-decidualized outer stroma. 2-[125I]Iodomelatonin binding sites were not seen in the mesometrial stromal cells during pregnancy. The role of ovarian hormones in the regulation of uterine melatonin receptors was examined by studying the binding at various phases of the estrous cycle, after ovariectomy with and without follow-on treatment of estradiol (E2), progesterone (P4) or both. 2-[125I]Iodomelatonin binding in the rat uterus fluctuated during the estrous cycle, being lowest during metestrus. Ovariectomy caused an almost 70% reduction of 2-[125I]iodomelatonin binding compared with the control. Injections of ovariectomized (OVX) rats with E2 or P4 alone or in combination for 11 days induced a partial restoration of 2-[125I]iodomelatonin binding in the OVX rats. The results show that mt1 melatonin receptors in the rat antimesometrial stroma are regulated by ovarian hormones.

Environment and sex determination in farmed fish

A certain plasticity of gonadal sex differentiation was reported in the 1930s following exogenous steroid treatments in fish, but demonstration that some environmental factors (temperature, pH, density and social interactions) can influence the sex ratio in gonochoristic species, is relatively recent. In fish, as in reptiles and amphibians displaying environmental sex determination the main environmental factor influencing sex seems to be temperature (TSD = Temperature Sex Determination). In most of the thermosensitive species (some Atherinids, Poecilids, Cichlids, the tilapias, the goldfish, a Siluriform, a flatfish,...) the male to female ratio increases with temperature, and/or ovarian differentiation is induced by low temperatures. Conversely, in some rare species (Dicentrarchus labrax, Ictalurus punctatus), high temperatures may produce female-biased sex ratios and/or low temperatures promote male-biased sex ratios. In the case of the hirame Paralichthys olivaceus, both high and low temperatures induce monosex inale populations while intermediate temperatures yield a 1 :I sex ratio (U-shape curve). Fish show particularities in their TSD patterns since monosex populations are generally not produced at extreme temperatures, suggesting the existence of strong temperature/genotype interactions. In reptiles, amphibians as well as fish displaying TSD, temperature treatments must be applied at a critical sensitive period which is relatively similar to the hormone-sensitive period. In gonochoristic fish, steroid hormones with estrogens in females and II-oxygenated androgens in males, are probably key physiological steps in the regulation of the gonadal sex differentiation. Cytochrome P450-aromatase, an enzyme which catalyses the conversion of androgens to estrogens, seems to be a critical enzyme for ovarian differentiation. The molecular mechanisms of thermosensitivity have been addressed in only two species. In both the tilapia, Oreochromis niloticus and the hirame, aromatase gene expression is down-regulated by masculinizing-temperature treatments. Furthermore, in tilapia the gene expression of II [beta]-hydroxylase (a key enzyme involved in the synthesis of II-oxygenated androgens) does not appear to be affected by temperature treatments. (Texte integral)

Effects of sex steroids on gonadotropin (FSH and LH) regulation in coho salmon (Oncorhynchus kisutch).

The effect of steroid hormone treatment on coho salmon (Oncorhynchus kisutch) was examined. The cDNAs for coho salmon FSH beta and LH beta subunits were cloned and sequenced using reverse transcriptase PCR. Northern blot analysis revealed that a single transcript of 1 kb for each of these subunits was present in the pituitaries of vitellogenic and spermiating coho salmon. RNase protection assays (RPAs) were developed to quantify FSH beta and LH beta subunit transcript levels. For the RPAs, antisense RNA probes and sense RNA standards were prepared from a region of the cDNAs which spanned the signal peptide and a portion of the mature protein. These RPAs were used to examine the effects of exogenous steroids including testosterone, estradiol-17beta (E2) and 17alpha, 20beta-dihydroxy-4-pregnen-3-one (17alpha,20beta-P) in vivo, in coho salmon at three time points during the spring period of gonadal growth when plasma levels of FSH are increasing. Both testosterone and E2 increased steady state mRNA levels of LH beta, whereas E2 decreased steady state mRNA levels of FSH beta in one experiment. Thus, the RPAs were able to detect changes in steady state mRNA levels in response to exogenous steroid treatment. Plasma and pituitary levels of FSH and LH were also measured using RIA. Throughout the experimental series, FSH plasma levels decreased in response to exogenous testosterone and E2 administration, while 17alpha,20beta-P had no effect on FSH plasma levels. Plasma LH levels were not detected throughout the course of the experiment. Pituitary LH increased in response to testosterone and E2, while pituitary FSH levels did not change. 17alpha,20beta-P had no effect on pituitary FSH or LH content during the experiment. Thus, regulation of the gonadotropins in coho salmon occurs at both the transcriptional as well as the translational level. Testosterone and E2 appear to have negative feedback effects on FSH, but positive feedback on LH.

Behavioral and neurobiological effects of estrogen replacement therapy and a history of triphasic oral contraceptive exposure.

The effects of contraceptive steroids and estrogen replacement therapy on behavior and neuroendocrine function were evaluated in adult female cynomolgus monkeys. During the 'premenopausal' phase of the experiment, the animals were assigned to either treatment with a triphasic oral contraceptive (OC) for 24 months or the untreated control group. The monkeys were then ovariectomized and half of each of the premenopausal groups were randomly assigned to either treatment with conjugated equine estrogens (ERT) or the untreated control group for 12 months (the 'postmenopausal' phase). All evaluations were completed during the postmenopausal phase of the experiment. Both types of exogenous steroid treatments appeared to increase cardiovascular and hypothalamic-pituitary-adrenal responses to stress in socially dominant but not socially subordinate females. A history of triphasic OC administration increased contact aggression received, and reduced the prolactin response to fenfluramine, suggesting reduced serotonergic activity, for at least a year following the cessation of triphasic OC treatment.

Effects of axotomy and testosterone on androgen receptor mRNA expression in hamster facial motoneurons.

We have previously demonstrated that testosterone propionate (TP) treatment accelerates the rate of regeneration following facial nerve crush axotomy in adult male hamsters. These effects are mediated by androgen receptor (AR) activation and are blocked by pretreatment with the AR antagonist, flutamide. In addition to its beneficial effects on regeneration, TP regulates AR mRNA levels in facial motor neurons (FMN). Gonadectomized (gdx) male hamsters have been shown to have approximately 50% of the AR mRNA levels found in gonadally intact males. Administration of TP to gdx males results in an upregulation in AR mRNA levels after 1 day of treatment. Recent reports in the literature suggest that axotomy also may regulate the expression of AR in motor neurons. In this study, we examined the effects of axotomy and exogenous steroid treatment on the regulation of AR mRNA in hamster FMN. Five days after castration, adult male hamsters were subjected to a right facial nerve axotomy. Half the animals received one 10-mm Silastic capsule filled with 100% crystalline TP, and the remainder were sham implanted. Postoperative survival times were 6 h or 1, 2, 4, 7, or 14 days. In situ hybridization in conjunction with an AR riboprobe and computerized image analysis were used to quantify AR mRNA levels. The contralateral FMN served as internal controls for these experiments, and FMN of gonadally intact males served as additional nonaxotomized controls. As predicted, AR mRNA levels were upregulated in contralateral control FMN after TP treatment. However, this TP-induced upregulation of AR mRNA levels did not occur in the axotomized FMN. These results indicate that axonal injury can disrupt the normal regulatory pattern of AR mRNA expression by exogenous steroids in motoneurons. We conclude that the potentiation of regenerative events by TP does not require augmented synthesis of AR, but, instead, enhanced stabilization of existing receptors.

Testosterone Treatment of Men Treated With Glucocorticoids

GLUCOCORTICOIDS ARE used for immunosuppressive or anti-inflammatory treatment of a wide range of diseases, including nephrotic syndrome, asthma, rheumatoid arthritis, polymyalgia rheumatica, various vasculitides, atopic dermatitis, and inflammatory bowel disease. Although glucocorticoids have shown beneficial effects on treating these diseases, long-term glucocorticoid treatment may have severe adverse effects; these side effects include osteoporosis and fracturing, diabetes mellitus, dramatic weight gain, accelerated atherosclerosis, hypertension, and decreased muscle mass and strength (steroid-induced myopathy).1In fact, the Cushing syndrome that is produced by exogenous steroid treatment can, in some instances, be worse than the disease that is being treated. It has been estimated that the prevalence of vertebral fractures in asthmatic patients who receive oral glucocorticoids for at least 1 year is 11% and that 30% to 35% of patients who take oral glucocorticoids for prolonged periods will experience a vertebral fracture.2In previous studies, oral prednisone (10-25 mg) that was

Characterization of ovarian follicular cysts and associated endocrine profiles in dairy cows.

It is generally accepted that ovarian follicular cysts (cysts) are nonovulatory follicular structures that contribute to extended calving intervals. Follicle/cyst dynamics and the etiology of cysts are unclear. The present study was conducted to characterize follicle/cyst dynamics and to define endocrine changes (etiology) associated with cyst development. Thirty-two dairy cows were studied: controls (n = 6), cows with spontaneously occurring cysts (n = 14), and cows in which cysts were induced by exogenous steroid treatment (n = 12). Ovaries of cows were scanned daily by ultrasonography to record follicle/cyst dynamics. Blood was collected to determine endocrine changes associated with follicle/cyst life span. Three ovarian responses in cows with cysts were observed: persistence of cysts, turnover of cysts, or spontaneous recovery (self-recovered; turnover of cysts and replacement with a follicle that ovulated). Mean maximum size of cysts was larger (p < 0.05) than that of ovulatory follicles (2.80 +/- 0.19 vs. 1.60 +/- 0.05 cm). Mean interval from initial detection of follicle/cyst wave to detection of a new follicle/cyst wave in cows with cysts was longer (13.0 +/- 1.1 days; p < 0.05) and more variable (6 to 26 days; p < 0.05) than in controls (8.5 +/- 0.5 days and 6-14 days, respectively). Cysts grew at the same rate as follicles but continued to grow for an additional period of time. A transient increase in FSH preceded detection of all follicle/cyst waves.(ABSTRACT TRUNCATED AT 250 WORDS)