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PubMed1988

Epididymal sperm profiles in young adult, middle-aged, and testosterone-supplemented old rats.

Both ejaculated semen and epididymal contents from an individual male contain sperm that differ in various physicochemical characteristics. An experiment is reported in which epididymides from rats 5-24 months old were subjected to density gradient centrifugation to separate gametes of different stages of maturity. The research was designed to examine typical changes in "profiles" of sperm maturity during the reproductive lifetime of rats. Also, testosterone complexed with cyclodextrin that mimics the episodic release of the endogenous hormone was used to supplement the decreased circulating titers of some of the old males. Results revealed clear ontogenetic patterns of gradually decreasing reproductive competence as measured by absolute numbers of sperm, circulating levels of testosterone, and various other physiological markers of fertility. Sperm profiles also revealed age-specific changes with a shift toward progressively more mature, perhaps senile, gametes that begins at middle age. Testosterone supplementation (400 micrograms/kg b.w./day for 30 days) failed to restore sperm numbers or other measures of physiology in the old males, but the steroid modified sperm profiles to approximate more closely the profiles characteristic of young adult males than either untreated middle-aged or old males. The data were interpreted as suggesting that epididymal sperm profiles clearly identify males of different ages, and that the aging epididymis retains its capacity to respond to manipulations that modify the endocrine milieu.

Aging↗

PubMed1986

Changes in gonadotropin and ovarian steroids associated with oocytes maturation during spawning induction in the carp.

The present study correlates the profiles of certain ovarian steroid hormones with stages of oocyte maturation in common carp induced to spawn by classic hypophysation. Sixteen females were injected at midday with a calibrated homologous pituitary extract (cPE) containing 0.07 mg immunoreactive cGTH/kg body wt, as a priming dose. Ten of those females were injected 11 hr later with cPE containing 0.35 mg IR cGTH/kg body wt as an induction dose (Group P + IN). The other females were left without further treatment (Group P). An additional 6 fish were injected around midnight with the induction dose only (Group IN). A control group was injected with 0.7% saline (0.2 ml/kg) at midday and at midnight (Group S). Ovarian biopsies were taken at intervals and the maturational stages of individual females were recorded. Blood was sampled simultaneously with the biopsies. GTH, estradiol (E2) and 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17,20-P) were determined by specific RIAs. Germinal vesicle breakdown (GVBD) and ovulation were observed only in Group P + IN 2-4 hr after the second injection. The change in circulating ovarian steroids, in response to hypophysation, was found to depend on the maturational stage of the oocytes. Fish with oocytes showing central and eccentric GV responded to the increased GTH level by elevating E2, but not 17,20-P in the circulation. However, fish with ovaries containing peripheral GV responded by an increase in circulating 17,20-P (111 +/- 14.6 ng/ml) concomitantly with a transient decrease in E2. Only fish that showed such a shift in the steroidogenic profile exhibited GVBD in their oocytes and consequently ovulated. This finding is consonant with the hypothesis that 17,20-P is the maturational-inducing steroid in the carp.

Animals↗

PubMed2001

Regulation of steroidogenic acute regulatory protein expression and progesterone production in endometriotic stromal cells.

The regulation of steroidogenic acute regulatory protein (StAR) gene expression and the synthesis of steroids from cholesterol in ectopic endometriosis tissues were investigated. Peritoneal fluid and endometrial tissues were collected from patients with endometriosis and otherwise healthy women. Peritoneal progesterone and 17 beta-E2 concentrations were highest in early stage endometriosis compared with those in advanced stage endometriosis and in normal women. In concordance with the profile of peritoneal steroids, StAR mRNA and protein were greatest in ectopic implants of early endometriosis. In the advanced stage, concentrations of StAR mRNA and protein were also greater compared with those in normal endometrium. In contrast, P450 side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase transcripts were not different between normal endometrium and ectopic endometriotic implants. Expression of StAR mRNA was detected in purified stromal, but not epithelial, cells. Treatment with PGE(2), but not TNF alpha, or IL-1 beta significantly increased StAR expression and thus induced progesterone production in cultured endometriotic stromal cells. These results demonstrated that aberrant expression of StAR in ectopic endometriotic tissues leading to increased peritoneal progesterone is associated with the formation of endometriosis. Induction of StAR gene expression by peritoneal PGE(2) in endometriotic stromal cells may further contribute to the development of endometriosis.

Ascitic Fluid↗

PubMed1980

The early recognition of the 21-hydroxylase deficiency variety of congenital adrenal hyperplasia.

The urinary steroids excreted by three newborn infants with 21-hydroxylase deficiency and by 15 healthy newborns aged two days have been compared after analysis by gas liquid chromatography (GLC). The identity of each steroid was carefully checked by gas chromatography/mass spectroscopy (GC-MS). The enzyme deficiency leads to the elevated excretion of urinary precursor metabolites, mainly 3alpha,17alpha,20alpha-trihydroxy-5beta-pregnan, 3alpha,17alpha,20alpha-trihydroxy-5beta-pregnan-11-one and 3alpha,17alpha-dihydroxy-5beta-pregnan-20-one. In the search for a quick and firm confirmation of suspected 21-hydroxylase deficiency in a newborn baby by means of a GLC-profile of urinary steroids, most attention has up to now been paid to 3alpha,17alpha,20alpha-trihydroxy-5beta-pregnan. However, 3alpha,17alpha-dihydroxy-5beta-pregnan-20-one is a better indicator, as it enables one to confirm the existence of this disease soon after birth directly from the GLC-profile without further analyses by GC-MS.

Adrenal Hyperplasia, Congenital↗

PubMed1994

Androgen binding sites in peripheral human mononuclear leukocytes of healthy males and females.

Androgen binding sites have been identified in circulating human mononuclear leukocytes of healthy donors of both sexes. Cells were separated from blood samples on a Ficoll gradient and incubated with different concentrations of [3H]testosterone in the presence or absence of a 400-fold excess of unlabelled testosterone. Binding data were derived from Scatchard analysis. The binding sites fulfil the required criteria for specific steroid binding sites however differ somewhat from the classic androgen receptors from genital skin fibroblast: in fertile adult males (n = 20) the binding sites showed (1) a high affinity for testosterone (1.32 +/- 0.49 nM; mean +/- SD), (2) a saturable capacity (184 +/- 52 binding sites per cell; mean +/- SD), and (3) a characteristic competitive binding profile for other steroid hormones (relative binding affinities: testosterone = dihydrotestosterone > 17 beta-estradiol > progesterone, whereas aldosterone, 17-hydroxy-progesterone and cortisol did not compete appreciably). Furthermore the number of binding sites determined using [3H]dihydrotestosterone, [3H]RU-1881, or [3H]testosterone were comparable. This raises the possibility that androgen receptors in peripheral mononuclear leukocytes differ from those in genital skin fibroblasts. There was no apparent correlation between serum testosterone concentrations and androgen binding sites. In fertile women remarkable changes in androgen binding sites were seen in the course of the menstrual cycle, with a significant increase in the immediate preovulatory period. The presence of androgen receptors in peripheral mononuclear leukocytes provides for the first time the experimental basis for an hypothesis of direct, receptor-mediated effects of androgens on mature immunocompetent cells. The immunological implications of these results are discussed.

Adult↗

PubMed1998

Insulin sensitivity and sex steroid hormone levels during the menstrual cycle in healthy women with non-insulin-dependent diabetic parents.

OBJECTIVE: To identify the effect of the menstrual cycle and sex steroid hormone levels on insulin sensitivity in healthy women with non-insulin-dependent diabetic parents. METHODS: A clinical trial was realized in 6 healthy women with non-insulin-dependent diabetic parents and in 6 control subjects. In both phases of the menstrual cycle the following tests were made: insulin tolerance test, metabolic profile, and sex steroid hormone levels. RESULTS: Insulin sensitivity was significantly lower in the follicular (p = 0.004) and luteal (p = 0.01) phases of the menstrual cycle in probands compared with controls. In the luteal phase dehydroepiandrosterone was higher in probands than in controls (p = 0.009). CONCLUSIONS: Healthy women with non-insulin-dependent diabetic parents had a lower insulin sensitivity in both phases of the menstrual cycle compared with the control group. Dehydroepiandrosterone was higher in the luteal phase in probands than controls.

Adult↗

PubMed1976

Pituitary and ovarian function in women with vesicovaginal fistuale after obstructed and prolonged labour.

This study concerns 11 patients with menstrual disorders dating back to an obstructed and prolonged labour, and 5 women with similar histories but without menstrual disorders. All patients were able to secrete gonadotrophins. According to the gonadotrophin pattern, the patients could be divided into three groups: in the amenorrhoeic and in 2 normally menstruating women various degrees of suppression of basal and peak levels of luteinising hormone (LH) could be observed; patients with infrequent menstrual periods showed temporarily arrested secretion of gonadotrophins and ovarian steroids; and in polymerrhoea a non-cyclic but high secretion was seen. The gonadotrophin response to oestrogen levels was temporarily or permanently disordered in all but 3 patients in this series, whereas an ovarian refractoriness to gonadotrophins was only infrequently observed. There were 2 cases of 'ovulatory amenorrhoea' as judged by the normal profiles of ovarian steroids. Biopsies indicated inadequate endometrial transformation in many cases of amenorrhoea. Abnormal responses to the stimulatory tests of pituitary secretion of human growth hormone (HGH) and/or LH were seen in 6 patients. The study suggests that menstrual disorders after obstructed labour are associated with derangement of different hypophyseotrophic areas of the hypothalamus.

Adrenocorticotropic Hormone↗

PubMed2004

Changes in testicular and nipple volume related to age and seasonality in Japanese macaques (Macaca fuscata), especially in the pre- and post-pubertal periods.

We investigated, longitudinally and cross-sectionally, age and seasonal change in both the testis and nipple volume of Japanese macaques (Macaca fuscata) in relation to concentration profiles of gonadal steroids: testosterone (T) in males and progesterone (P) in females. Testicular volume (TV) and nipple volume (NV) showed rapid growth at puberty, 4.5 and 3.5 years of age in males and females, respectively, but in both sexes there were precocious individuals. The testis as a whole matures at about 10 years of age. TV change is closely related to T concentration profile. The pattern of TV change is composed of maturation and seasonal effects, with individual variation evident mainly in the latter. Some individuals show a simple pattern consisting of one peak in the breeding season (from summer to winter) and one trough in the non-breeding season. Other individuals exhibit a more complicated pattern composed of two or more peaks and troughs before and during the breeding season. The nipple matures at about 7 years but it is difficult to determine the exact maturational age as there are many confounding factors relating to NV. NV shows seasonal fluctuations similar to that of TV. Many animals have periods of substantial growth whereas others do not. The NV in adults from 10 to 25 years does not appear to change much with age, but animals older than 25 years of age have significantly smaller nipples. Seasonal fluctuation in NV mirrors that of the P level. Considered to be controlled by estrogen and P, the NV is a good indicator of the physiological status of reproduction, with its peak about 2 weeks earlier than that of P, that is, at the mid-follicular phase. NV and P level show a similar pattern in pregnancy; from conception, indicated by a P peak, NV and P concentration first decrease, then they increase until peri-parturition and slowly decrease again until the next breeding season.

Aging↗

PubMed1990

Steroid determinations in human ovarian follicular fluid using capillary gas chromatography.

A method is presented based on capillary GLC using both a thermionic and a flame ionization detector to simultaneously analyse all major unconjugated steroids in ovarian follicular fluids (FF). Although specificity can not always be guaranteed for the smaller concentrations of androstenedione and cortisol, accuracy and reproducibility are excellent for the major progestagens and estrogens (progesterone, 17- and 16 alpha-hydroxyprogesterone, pregnenolone, 20 alpha-dihydroprogesterone, estradiol and estrone). Above all the analysis is performed with relatively cheap instrumentation and products. Apart from the "profiles" of unconjugated steroids, a semi-quantitative analysis of steroid conjugates is possible if a preliminary group separation with disposable anion exchanger columns is included.

17-alpha-Hydroxyprogesterone↗

PubMed1989

[Plasma dehydroepiandrosterone sulfate and urine steroid excretion in hepatic cirrhosis].

In the present study we evaluated the alterations of plasma levels of dehydroepiandrosterone sulphate (DHEA-S) and of steroid-derivatives urinary excretion in cirrhotic patients compared with normal controls. 107 patients have been studied: 45 affected by liver cirrhosis (22 males and 23 females) both in compensated and in ascitic state, and 62 healthy controls (32 males and 30 females). In all patients we assayed plasma DHEA-S by RIA as well as common liver function tests; moreover gaschromatographic profile of adrenal steroid excretion was performed in daily urine. Our findings show a significantly lower DHEA-S in cirrhotic patients compared with healthy controls, both males (451.7 SD 440.3 ng/ml vs 1438.3 SD 604.8, p less than 0.001) and females (225.5 SD 152.6 ng/ml vs 974.0 SD 405.7, p less than 0.001). Variance analysis confirmed that the difference was significant both for compensated and uncompensated ones. We also found some interesting relationships between DHEA-S and liver function tests, cholesterol and age. Urinary steroids were markedly low in both sexes, particularly adrenal sexual fraction. Our data show clear disfunction in DHEA-S metabolism in liver cirrhosis, partially related with the severity of the disease.

Adult↗

PubMed2000

Non-steroidal anti-inflammatory drugs with different cyclooxygenase inhibitory profiles that prevent aberrant crypt foci formation but vary in acute gastrotoxicity in a rat model.

BACKGROUND: Standard non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of colorectal cancer; however, their use as preventive agents is limited by their inherent toxicity. Drugs that selectively inhibit cyclooxygenase-2 (COX-2) may be useful in this setting as they are supposedly less toxic. No study has directly compared the ability of standard NSAIDs and selective COX-2 inhibitors to inhibit colorectal cancer at clinically relevant doses. METHODS: Aberrant crypt foci (ACF) were induced in Sprague-Dawley rats by using 1,2-dimethylhydrazine (DMH). Test agents or vehicle were then administered for 3 weeks, twice daily through orogastric gavage. At the end of this period, the number and multiplicity of ACF were determined. The agents tested at equivalent anti-inflammatory doses were: sulindac and indomethacin (standard NSAIDs), meloxicam (selective COX-2 inhibitor), celecoxib (specific COX-2 inhibitor) and sulindac sulfone (no known COX activity). Acute gastrotoxicity of NSAID in rats was compared by using quantitative histology. RESULTS: All test agents reduced the number of ACF. There was a 42% reduction with indomethacin, 46% with sulindac, 46% with meloxicam, 22% with celecoxib and 36% with sulindac sulfone. Only the COX-2 inhibitors caused no significant gastrotoxicity in rats. CONCLUSIONS: Cyclooxygenase-2 inhibitors are potentially ideal chemopreventive agents as they inhibit ACF and are not gastrotoxic.

Acute Disease↗

PubMed1993

Cloning and expression of the gene from Candida albicans that encodes a high-affinity corticosteroid-binding protein.

We have previously demonstrated the presence of a corticosteroid-binding protein (CBP) in Candida albicans and speculated on its homology to the glucocorticoid receptor. To explore this relationship further, we cloned the CBP gene. Our strategy employed sequencing enzymatically derived peptide fragments from purified CBP and using this information to synthesize degenerate oligonucleotide primers for use in the PCR. A 117-bp fragment amplified from C. albicans DNA was then used to screen a genomic library. Hybridizing clones were isolated, and DNA sequencing revealed an open reading frame of 1467 bp which encoded a protein with a molecular weight of 55,545. Southern analysis demonstrated that the gene was present at a unique locus within chromosome R of the Candida genome, while Northern analysis showed that the gene was expressed in C. albicans as a 1.8-kb transcript. CBP was over-expressed in Saccharomyces cerevisiae, and it exhibited an apparent dissociation constant (Kd) of 7 nM for [3H]corticosterone and displayed a steroid hormone binding profile comparable to that of the native protein. Searches of the data banks revealed little overall similarity to other cloned genes. However, the amino acid sequence contains a dinucleotide-binding fingerprint. In conclusion, we have cloned the gene encoding the CBP from C. albicans and have shown that the expressed protein has the properties of the native CBP. A comparison of the cloned gene to members of the steroid-thyroid-retinoic acid receptor gene superfamily showed that CBP is unrelated to these hormone receptors.

Adrenal Cortex Hormones↗

PubMed1991

Cardiovascular effects of Org OD 14--a new steroidal therapy for climacteric symptoms.

The cardiovascular effects of Org OD 14, a synthetic steroid which relieves climacteric symptoms without stimulating the endometrium, were assessed in a group of healthy post-menopausal women. Limb blood flow was measured by venous occlusion plethysmography. Resting forearm blood flow, the dilator response to anoxic exercise and heart rate increased significantly after six weeks of drug treatment. Hand flow was unchanged. The cardiovascular effects of Org OD 14 differ from those seen with oestrogens, in keeping with the unique pharmacological profile of this steroid.

Blood Pressure↗

PubMed1995

Androgen, estrogen, and progesterone receptors in normal and aging prostates.

Testicular hormones regulate the growth and development of the prostate. The presence of androgen receptors in prostatic tissue and their importance in the normal development of the prostate has been established. Age-related changes in the hormonal milieu, and perhaps steroid hormone receptor profile, could set in motion pathological changes leading to the onset of benign prostatic hyperplasia (BPH) or prostate cancer which primarily affect older men. The accumulation of dihydrotestosterone with age, the reawakening of the inductive potential of the prostatic stroma, the altered rate of apoptosis with age, and the age-related changes in the ratio of testosterone:estrogen have all been implicated in the etiology of BPH. In addition to androgen receptors, several studies have documented the presence of estrogen and progesterone receptors in BPH and prostate cancer. So far, most studies have focussed on the correlation between the presence/absence of steroid hormone receptors and response to hormonal therapy. The molecular mechanisms by which these steroid hormone receptors regulate the onset or progression of BPH and prostate cancer are not yet clear. The chronological changes in the levels and distribution of steroid hormone receptors in normal prostatic tissue and the effect of such changes on the synthesis of growth factors, growth factor receptors, and oncogenes should be investigated.

Aging↗

PubMed1984

[Cytoplasmatic receptors of steroid hormones in malignant epithelial ovarian tumors].

The levels of estrogen, progesterone, androgen and glucocorticoid receptors were assayed in 70 malignant epithelial tumors of human ovaries. The percentage of progesterone, androgen and glucocorticoid receptor-positive tumors was significantly higher in reproductive patients than in menopausal ones. Well-differentiated serous cystadenocarcinomas showed a higher level of progesterone receptors than those characterized by poor differentiation of cells. It was found that steroid hormone receptor profile of primary tumor may be determined in its metastases into the greater omentum whenever tumor cannot be removed. In cases of preoperative chemotherapy, the percentage of receptor-positive ovarian tumors was lower.

Adult↗

PubMed1990

Sex steroid changes in porcine cystic ovarian disease.

Ten sex steroids were measured in the peripheral serum and ovarian follicular fluid of female pigs with or without cystic ovarian disease. In general, progestin, especially progesterone, accumulated excessively in the fluid contained in cystic compared with normal follicles. Nonluteinized cystic follicles contained up to four times the progesterone concentration found in large normal preovulatory follicles. Levels of this steroid increased with luteinization of cystic follicles to as much as 10 times those found in large preovulatory follicles. In contrast, the concentration of follicular fluid androgens and estrogens in cystic follicles were, at best, barely detectable (5 to 10 pg/ml). These results are indicative of a steroidogenic blockade in the conversion of C21 progestin to C19 androgens and C18 estrogens in the cystic follicles. In spite of an enormous accumulation of follicular progestin and subnormal concentration of androgens and estrogens, circulating levels of these hormones in pigs bearing cystic ovaries were in the normal range for cycling sows. Clearly, the hormonal abnormalities in the cystic follicles are not reflected in the serum profiles of these steroids.

Androgens↗

PubMed2003

Measures of aggression and mood changes in male weightlifters with and without androgenic anabolic steroid use.

Supraphysiologic doses of testosterone are associated with increased aggression that is hypothesized to be a function of testosterone serum concentrations, mood, and personality. The study attempted to characterize this relationship among weightlifters who were users (n = 10) and nonusers (n = 18) of anabolic steroids. Participants were interviewed using the Modified Mania Rating Scale and Hamilton Rating Scale for Depression to assess mood, the Buss-Durkee Hostility Inventory (BDHI) and Point Subtraction Aggression Paradigm (PSAP) to assess aggression, and the Personality Disorder Questionnaire (PDQ-R) to assess personality. Blood samples were obtained for the determination of total, free, and weakly bound testosterone. Comparisons of continuous variables between testosterone users and non-users were performed with a parametric (unpaired t-test) or non-parametric (Mann-Whitney) test where appropriate. Correlations with testosterone were examined separately for testosterone users and non-users, using Spearman rank correlation. The subjective (BDHI) and objective (PSAP) assessments of aggression found that supranormal testosterone concentrations were associated with increased aggression. However, the PDQ-R results suggest that this finding was confounded by the personality disorder profile of the steroid users, because steroid users demonstrated Cluster B personality disorder traits for antisocial, borderline, and histrionic personality disorder.

Adult↗

PubMed1988

Occult ovarian failure: a syndrome of infertility, regular menses, and elevated follicle-stimulating hormone concentrations.

Ten women with infertility, regular menses, and elevated plasma FSH concentrations after a failed in vitro fertilization attempt were studied throughout a spontaneous menstrual cycle. Plasma estradiol, progesterone, inhibin, LH, and FSH concentrations were measured by RIA on days 1, 8, 15, and 22 and compared with the ovarian steroid and gonadotropin profiles obtained from seven endocrine-normal women. The elevated FSH concentrations in the hypergonadotropic group were not associated with significant changes in E2 and P4, but an increase in LH concentrations was found on days 1, 8, and 22 (medians of 18 and 4, 17 and 6, and 7 and less than 3 U/L for the hypergonadotropic and normal groups, respectively; P less than 0.01). Their plasma inhibin concentrations [213, 242, 747, and 561 U/L (median values on days 1-7, 8-14, 15-21, and 22-28)] were normal. Autoantibodies to adrenal, thyroid, or ovary were present in five (50%) women, and antiovarian antibodies were present in 4. Two women gave a family history of thyroid disease, and one woman was hypothyroid. Repeat assessment 3-6 months revealed persistently elevated FSH concentrations in five (63%) of eight women; the other three had normal ovarian steroid and gonadotropin concentrations. The triad of infertility, regular menses, and elevated plasma FSH concentrations describes a group of women with occult ovarian failure, a condition of compensated granulosa cell function, which may be an early stage of premature ovarian failure. These women with occult ovarian failure had an impaired response to ovarian hyperstimulation and may be at increased risk of developing polyglandular autoimmunity.

Adult↗