Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- Study the seasonal steroid hormones of common carp in Caspian Sea, Iran. [JOURNAL ARTICLE]
- Springerplus 2013 Dec; 2(1):193.
In this investigation, serum steroid hormones such as testosterone (T), 17β-estradiol (E2) and progesterone (P) in 12 female of the migratory population of Common carp (Cyprinus carpio) in southeast of Caspian Sea during a year from May 2011 to May 2012 were studied. The results of present study revealed that changes in levels of steroid hormones, (E2) and (T) were closely correlated to ovarian development. There was significant difference in level of 17 β- estradiol between autumn and winter seasons that the highest of 17-β estradiol level was observed in autumn season. In the case of progesterone hormone, higher levels was recorded in summer season and there was significant difference between summer and spring seasons and lower level of testosterone was observed in spring season.
- Impact of polymorphisms in the oestrogen receptors alpha and beta (ESR1, ESR2) genes on risk of vasculogenic erectile dysfunction. [JOURNAL ARTICLE]
- Andrology 2013 May 20.
Erection is principally a vascular phenomenon. Oestrogen affects the vascular system in various ways. Oestrogen effects are mediated by oestrogen receptors (ERs). We examined the relationship of two polymorphisms in ESR-α (ER-1) (rs2234693 and rs9340799) and two polymorphisms in ESR-β (ER-2) (rs4986938 and rs1256049) with risk of vasculogenic erectile dysfunction (VED). The rs2234693 (ER-α PvuII), rs9340799 (ER-α XbaI), rs4986938 (ER-β AluI) and rs1256049 (ER-β RsaI) were genotyped using polymerase chain reaction-restriction fragment length polymorphism technique. Serum levels of sex hormone-binding globulin (SHBG), total testosterone, free testosterone (fT), total oestradiol (E2) and free oestradiol (free E2) were also measured. A total of 266 men with VED and 532 healthy controls were recruited into this study. The ER-α PvuII C allele (OR = 4.2; 95% CI: 2.79-8.43, p = 0.001), ER-α XbaI A allele (OR = 4.87; 95% CI: 2.75-8.64, p = 0.001), ER-β RsaI A allele (OR=0.37; 95% CI: 0.24-0.66, p = 0.001) and ER-β AluI A allele (OR = 0.29; 95% CI: 0.16-0.57, p = 0.001) were significantly associated with VED. Subjects with ER-α PvuII CC and ER-α XbaI AA genotypes had highest serum levels of E2, and subjects with ER-β RsaI AA and ER-β AluI AA genotypes had lowest serum levels of E2. Patients with lower serum levels of E2 had more sever VED and more mixed vascular type VED. In haplotype analysis, PvuII C-XbaI A increased the risk of developing VED by more than eightfold, in contrast, RsaI A-AluI A haplotype had protective effect (OR = 0.53; 95% CI: 0.34-0.76, p = 0.002). The ER-α and ER-β gene polymorphisms and haplotypes are associated with presence, type and severity of VED.
- Effects of testosterone treatment on bone mineral density in men with testosterone deficiency syndrome. [JOURNAL ARTICLE]
- Andrology 2013 May 20.
The decline in testosterone levels found in men with testosterone deficiency syndrome (TDS) is associated with a decrease in bone mineral density (BMD). To study the safety profile and efficacy of testosterone treatment on BMD in patients with TDS. In this 2-year prospective open-label study, patients were administered 50 mg of testosterone gel daily (adjustable after 3 months up to 75-100 mg or down to 25 mg) for 12 months, followed by treatment with 1000 mg of testosterone undecanoate every 2-3 months from months 12-24. Outcome measures were as follows: (i) Changes in clinical chemistry safety parameters and total testosterone, sex hormone binding globulin and calculated free testosterone (cFT) levels; (ii) Changes in Aging Males' Symptoms Scale (AMS) and International Prostate Symptom Score scores; and (iii) Changes in lumbar spine and hip BMD. A total of 50 men aged 50-65 years with TDS (AMS >26 and cFT <0.250 nmol/mL) took part in the study. There was no significant impact of testosterone on safety. Prostate-specific antigen and haematopoietic parameters increased significantly, although the changes were not clinically significant. Total and cFT increased significantly after 3 months (p < 0.001) and there were significant improvements after 3 months in AMS scores (p < 0.001). BMD improved significantly in L2-L4 (2.90 and 4.5%), total femur (0.74 and 3%) and trochanter (1.09 and 3.2%) at 12 and 24 months respectively. Testosterone treatment in men with TDS has a good safety profile, leads to significant improvement in lumbar spine and hip BMD, and improves symptoms, as assessed by the AMS questionnaire.
- Supplementation with Vitamin D Does not Increase Serum Testosterone Levels in Healthy Males. [JOURNAL ARTICLE]
- Horm Metab Res 2013 May 17.
Cross-sectional studies indicate a positive relation between serum 25-hydroxyvitamin D [25(OH)D] and testosterone. It is not known if this relation is causal, which in theory could be in both directions. A cross-sectional population based study was designed with pooled data from 3 vitamin D randomized clinical trials (RCTs) performed in Tromsø with weight reduction, insulin sensitivity, and depression scores as endpoints, and one testosterone RCT in subjects with low serum testosterone (<11.0 nmol/l) and with body composition as endpoint. Serum 25(OH)D and androgens were measured in 893 males in the cross-sectional part, at baseline and after 6-12 months of supplementation with vitamin D 20 000 IU-40 000 IU per week vs. placebo in the vitamin D RCTs (n=282), and at baseline and after one year treatment with testosterone undecanoate 1 000 mg or placebo injections (at baseline and after 6, 16, 28, and 40 weeks) in the testosterone RCT (n=37). In the cross-sectional study, serum 25(OH)D was found to be a significant and positive predictor of serum testosterone. In the vitamin D RCTs, no significant effect on serum total or free testosterone levels was seen, and in the testosterone RCT no significant effect on serum 25(OH)D was seen. This was unchanged in sub-analyses in subjects with low serum 25(OH)D (or testosterone) levels. In conclusion, in subjects without significant vitamin D deficiency, there is no increase in serum testosterone after high dose vitamin D supplementation. Similarly, in subjects with moderately low serum testosterone levels, substitution with testosterone does not increase serum 25(OH)D.
- Crizotinib for the treatment of non-small-cell lung cancer. [Journal Article]
- Am J Health Syst Pharm 2013 Jun 1; 70(11):943-7.
The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, and dosage and administration of crizotinib in the management of non-small-cell lung cancer (NSCLC) are reviewed.Crizotinib (Xalkori, Pfizer Inc.) is a novel tyrosine kinase inhibitor approved for the treatment of patients with locally advanced or metastatic NSCLC who exhibit assay-confirmed mutations of the gene coding for anaplastic lymphoma kinase (ALK). The primary biochemical mechanism of crizotinib is to inhibit ALK expression, leading to increased cell proliferation and decreased apoptosis. Crizotinib is metabolized and excreted after O-dealkylation by cytochrome P-450 (CYP) isoenzyme 3A4/5; as crizotinib is also an inhibitor of CYP3A4/5, its use entails a high potential for drug interactions, including confirmed interactions with ketoconazole and rifampin that can alter crizotinib pharmacokinetics. A Phase I trial involving patients with ALK gene mutation-positive NSCLC demonstrated significant disease control with oral crizotinib use, including an overall eight-week response rate of 87% and an estimated six-month survival of 72%. At the standard dosage of 250 mg twice daily, crizotinib is well tolerated. In clinical trials to date, the most common grade 1 or 2 adverse events were nausea, diarrhea, vomiting, and visual disturbances; more severe toxicities included transaminase elevations (less than 7% of patients) and pneumonitis (less than 2% of patients). Hypogonadism leading to low testosterone levels appears to be universal among male patients treated with crizotinib.Crizotinib appears to be efficacious and well tolerated in patients with NSCLC and may have future potential applications in treating lymphomas and other cancers driven by ALK or c-MET gene mutations.
- The SUBITO-DE study: sexual dysfunction in newly diagnosed type 2 diabetes male patients. [JOURNAL ARTICLE]
- J Endocrinol Invest 2013 May 20.
Introduction No data on the prevalence of erectile dysfunction (ED) in subjects with newly diagnosed DM type 2 are currently available. Aim The aim of the present study was to estimate the prevalence of ED and its associated causes in a sample of male patients with recently diagnosed DM (<24 months) attending a diabetes care center. Methods The study comprised two phases: a cross-sectional analysis and a longitudinal reassessment of the data collected during the first phase. During the first phase 1503 subjects (mean age, 58.7±8.9 years) from 27 centers were interviewed: 666 (43.3%) reported experiencing ED, 499 of which (mean age, 58.8±8.8 years) agreed to participate in the study (final enrolment rate, 33.3%). Concurrent morbidities were hypertension (55.3%), dyslipidemia (39.5%), and coronary heart disease (7.8%); chronic complications were neuropathy (8.9%), nephropathy (12.6%) and retinopathy (7.6%) in about one third of the sample at enrolment. Results Overall, about 20% of the patients reported having used ED drugs, but more than 50% had abandoned therapy because of the drug's ineffectiveness or high cost. The prevalence of hypogonadism was 46.9% (total testosterone level, 3.5 ng/ml). Some 20% of patients reported symptoms suggestive of depression. Conclusion The present study provides data showing a high prevalence of ED, hypogonadism and depressive symptoms among male patients with newly diagnosed DM type 2. Further analysis of the data will elucidate the specific determinants of such conditions and their longitudinal significance.
- 11β-Hydroxyandrostenedione; the product of androstenedione metabolism in the adrenal; is metabolized in LNCaP cells by 5α-reductase yielding 11β-hydroxy-5α-androstanedione. [JOURNAL ARTICLE]
- J Steroid Biochem Mol Biol 2013 May 16.
11β-hydroxyandrostenedione (11OHA4), which is unique to the adrenal, was first isolated from human adrenal tissue in the fifties. It was later shown in the sixties that 11β-hydroxytestosterone (11OHT) was also produced by the human adrenal. Attention has shifted back to these adrenal androgens once more, as detection methods have enabled more accurate detection of steroid hormones. In this paper, we investigated the origin of these metabolites as well as their subsequent metabolism and examined a possible physiological role for 11OHA4 in prostate cancer cells. In H295R cells treated with forskolin and trilostane, etomidate, a reported CYP11B1 inhibitor, blocked the production of corticosterone, cortisol, 11OHA4 and 11OHT. The metabolism of androstenedione and testosterone by cytochrome P450 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) was assayed. Androstenedione was converted by CYP11B1, while the conversion by CYP11B2 was negligible. Both enzymes readily converted testosterone. The metabolism of these 11β-hydroxylated metabolites by 11β-hydroxysteroid dehydrogenase (11βHSD) type 1 and 2 was subsequently investigated. 11βHSD2 catalyzed the conversion of both 11OHA4 and 11OHT to their respective keto-steroids, while 11βHSD1 catalyzed the conversion of 11-ketoandrostenedione and 11-ketotestosterone to their respective hydroxy-steroids in Chinese hamster ovary cells. Investigating a functional role, steroid 5α-reductase type 1 and 2 converted 11OHA4 to 11β-hydroxy-5α-androstanedione (11OH-5α-dione), identified by accurate mass detection. UPLC-MS/MS analyses of 11OHA4 metabolism in LNCaP androgen-dependent prostate cancer cells, indentified the 5α-reduced metabolite as well as 11-ketoandrostenedione and 11-ketotestosterone, with the latter indicating conversion by 17β-hydroxysteroid dehydrogenase. Downstream metabolism by 11βHSD2 and by 5α-reductase may therefore indicate a physiological role for 11OHA4 and /or 11OH-5α-dione in normal and prostate cancer cells.
- [Cryptorchidism: medium- and long-term follow-up.] [JOURNAL ARTICLE]
- Minerva Pediatr 2013 Jun; 65(3):261-269.
Aim:Cryptorchidism represents the most frequent male genital anomaly in paediatric population and may potentially interfere with fertility and determine neoplastic testicular diseases. We wanted to evaluate the correlation between age at orchiopexy and follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone levels in adulthood, determining the long-term complications of surgical treatment.
Methods:Fifty-seven patients (mean age 19 years, range 18-27) surgically treated for cryptorchidism in pediatric age were included in a medium and long-term follow-up (10-19 years). We divided this population into four groups: A) monolateral cryptorchidism operated on before 36 months of age (15); B) monolateral cryptorchidism operated on over 36 months (32); C) bilateral cryptorchidism operated on before 36 months (5); and D) bilateral cryptorchidism operated on over 36 months (5). All patients underwent andrological examination, testosterone, FSH and LH dosage, measurement of testicular volume and spermiogram.
Results:Significant different FSH levels were found between group A and C and between A and D (P<0.01), while groups A and D presented also different mean testicular volume (P<0.01). In addition group D showed an abnormal morphology of spermiogram. The main complications found in follow-up were hydrocele (17,5%), varicocele (8,7%) and epididymal cysts (3.6%).
Conclusion:Monolateral cryptorchidism is associated with normal fertility when treated early (group A). Subjects in Group D, on the contrary, have a rise of FSH, a reduction of testicular volume and semen abnormalities. The long-term follow-up of these patients can also detect associated.
- Testosterone inhibits facilitating effects of parenting experience on parental behavior and the oxytocin neural system in mice. [JOURNAL ARTICLE]
- Physiol Behav 2013 May 14.
Parental behavior in mammals is facilitated by sensory experiences from infant, and by endocrine hormones. However, the interactions between these factors in the parental behavior of nonreproductive adults are not understood. We examined the interactive effects of gonadal hormones and the experience of repeated pup exposure on parental behavior in sexually naive mice. We also compared oxytocin (OT) expression levels in the paraventricular nucleus of the hypothalamus to behavioral outcomes. Clear sex differences were observed in retrieving tests; initial retrieving latency was shorter in females than in males, and 5-time pup exposure shortened retrieving latency in females only. Gonadectomy influenced neither initial retrieving latency nor pup sensitization in females. In contrast, gonadectomy shortened initial retrieving latency and caused pup sensitization in males. Estrogen implants given simultaneously with gonadectomy further shortened the initial retrieving latency in males, but pup sensitization was not affected and occurred in both sexes. In contrast, simultaneous testosterone implants impaired pup sensitization in both sexes. Similar to the results for responsiveness to pups, the number of OT neurons was increased by gonadectomy in males only. In comparison to gonadectomy only, OT neurons were decreased by simultaneous testosterone implants, but were not influenced by estrogen in either sex. Considering the parallel inhibitory effects of testosterone on both pup sensitization and number of OT neurons, we postulate that sex differences in parental responsiveness facilitated by repeated pup exposure were caused by an inhibitory effect of testosterone via the OT neural system in mice.
- Effects of Estradiol or Testosterone Treatment on Expression of Gonadotropin Subunit mRNAs and Proteins in the Pituitary of Juvenile Brown Hagfish, Paramyxine atami. [JOURNAL ARTICLE]
- Gen Comp Endocrinol 2013 May 16.
A single functional gonadotropin (GTH) comprising two subunits, αandβ, was recently identified in the pituitary of brown hagfish (Paramyxine atami). Little is known about the feedback mechanisms that regulate these GTH subunits by sex steroids in the hagfish. The present study was designed to examine feedback effects of estradiol and testosterone on mRNA expression and protein expression of both GTHα and GTHβ subunits in the pituitary of the juvenile P. atami. Intraperitoneal administration of estradiol over the course of 27 days resulted in substantial accumulation of immunoreactive (ir)-GTHα and ir-GTHβ in the adenohypophysis, but testosterone treatments over 27 days had no effects on ir-GTHα or ir-GTHβ. Estradiol treatment for 1, 2, 4 or 14 days had no effect on GTHα mRNA levels. In contrast, after 2 days of estradiol treatment, GTHβ mRNA levels had increased significantly from baseline, while these levels were not affected after treatment over 1, 4, or 14 days. After 14 days of testosterone treatment, both GTHα and GTHβ mRNA levels had decreased significantly from baseline levels. These results indicate that estradiol acted primarily to suppress the secretion of GTH, and hence resulted in the accumulations of ir-GTHα and ir-GTHβ in the pituitary. On the other hand, testosterone appeared to suppress both the synthesis and the secretion of GTH. Thus, estradiol and testosterone probably differ in their effects on the regulation of pituitary GTH synthesis and secretion in juvenile hagfish.