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Prevention of cholesterol cholelithiasis by dietary unsaturated fats in hormone-treated female hamsters.

We examined the effect of diet on gallstone incidence and the composition of biliary phosphatidylcholines in methyltestosterone-treated female hamsters. These hamsters were fed a nutritionally adequate purified lithogenic diet containing 2% corn oil, 4% butterfat, 0.3% cholesterol, and 0.05% methyltestosterone, resulting in a cholesterol gallstone incidence of 86%. This incidence was lowered when mono- and polyunsaturated fats or fatty acids were added to the diet: 2.5% oleic acid resulted in total prevention of cholesterol cholelithiasis, 2.5% linoleic acid, and 4% safflower oil (78% linoleic acid content) reduced gallstone incidence to 26 and 8%, respectively. An additional 4% butterfat (29% oleic acid content) produced gallstones in 50% of the animals. At the end of the 6-wk feeding period, the bile of all hamsters was supersaturated with cholesterol. The major biliary phosphatidylcholine species in all groups were (sn-1-sn-2): 16:0-18:2, 16:0-18:1, 18:0-18:2, 16:0-20:4, and 18:2-18:2. The safflower oil- and linoleic acid-fed hamsters exhibited an enrichment of 16:0-18:2 (16-18%); added butterfat or oleic acid increased the proportion of 16:0-18:1 (9 and 25%, respectively). We conclude that the phosphatidylcholine molecular species in female hamster bile can be altered by dietary fats/fatty acids and that mono- and polyunsaturated fatty acids play a role in suppressing the induced cholelithiasis.

Animal Feed↗

Androgen receptors in transitional cell carcinoma.

Androgen receptors were measured in transitional cell carcinoma tissues obtained from 13 patients with bladder tumours and 3 patients with ureteric tumours. Scatchard analysis of binding of mibolerone, a synthetic androgen, was used for receptor measurement. None of the patients were receptor positive. This study suggests that human male hormones do not play any direct role in the malignant transformation of human transitional cell epithelium.

Aged↗

Post-traumatic selective hypogonadotropic hypogonadism.

A very small proportion of hypopituitarism is due to head trauma, which may have occurred from days to years earlier. In the literature we found only three cases (two males, one female) of post-traumatic hypopituitarism in whom the hormone deficiency was claimed to be restricted to the gonadotrophs and considered to be permanent after a period of follow-up ranging from less than one year to four years. Here we describe a 26 yr-old male patient who, eight years after a motorcycle accident, was evaluated for hypogonadism and followed-up for three years. Serum testosterone, basal and GnRH-stimulated FSH and LH remained undetectable over the first 22 months of follow-up. Then, basal and GnRH-stimulated gonadotropins moved progressively into the normal range. Basal and dynamic evaluation of the other anterior pituitary hormones was persistently normal. At the 15th month of follow-up there was a change in the pituitary CT scan, presumably due to pituitary revascularization. Therefore, our patient disproves that post-traumatic isolated gonadotropin deficiency is irreversible.

Accidents, Traffic↗

[The latest developments in endocrinology 2004/2005].

The following review presents recent diagnostic and therapeutic developments in the field of endocrinology. With the development of strontium ranelate and teriparatide (human recombinant parathyroid hormone) two new drugs are now available for the treatment of postmenopausal osteoporosis. In addition, the therapeutic use of the calcimimetic agent cinacalcet in the treatment of primary and secondary hyperparathyroidism is discussed. The recent introduction of a novel, long-acting testosterone formulation (testosterone undecanoate) which only requires one intramuscular injection every 3 months, together with the already available hydroalcoholic testosterone gels, appear to be promising alternatives to the previous standard substitution therapy for male hypogonadism. Recently, the mineralocorticoid hormone aldosterone has gained much interest due to its central pathophysiological role in secondary hypertension and its potential deleterious role as a cardiovascular risk factor in nonepithelial target tissues. In this context, the therapeutic potential of a new selective mineralocorticoid receptor antagonist, eplerenone, will be ventilated. In addition, (18)F-DOPA positron emission tomography ((18)F-DOPA-PET), a new functional imaging modality for the diagnostic localization of chromaffin tumors, will be presented and the role of the somatostatin receptor radionuclide therapy with (90)Y-[DOTA](0)-Tyr(3)-octreotide ((90)Y-DOTATOC) for the treatment of advanced neuroendocrine tumors discussed. Furthermore, the ongoing controversy about the diagnosis and treatment of subclinical hypothyroidism will be summarized.

Adrenal Gland Neoplasms↗

A repeated 28-day oral dose toxicity study of 17alpha-methyltestosterone in rats, based on the 'enhanced OECD Test Guideline 407' for screening the endocrine-disrupting chemicals.

As part of the international validation project to establish the Enhanced OECD Test Guideline 407, we performed a 28-day repeated-dose toxicity study of 17alpha-methyltestosterone, an exogenous androgen agonist. Special attention was paid to the sensitivity of additional parameters for detecting endocrine-related effects of endocrine-disrupting chemicals, based on the existing Test Guideline 407. Seven-week-old Crj:CD(SD)IGS rats were allocated to one of four groups, each consisting of ten males and ten females, and 17alpha-methyltestosterone was administered daily by gavage at doses of 0 (control), 5, 20 and 80 mg/kg body weight per day. Male rats were killed on the day after the 28th administration and females on the day of the diestrus stage during the 4 day period after the 28th administration. Male rats receiving 80 mg/kg 17alpha-methyltestosterone demonstrated decreases in testis and epididymis weights, atrophy of seminiferous tubules and Leydig cells, and degenerated pachytene spermatocytes in the testes and degenerated germ cells in the epididymides as major alterations. Female rats showed abnormal estrous cycles, decreases in ovary and adrenal weights, increase in immature follicles with decreased corpus lutea in the ovaries at doses of 5 mg/kg and higher, as well as atrophy of zona reticularis in the adrenals and increase in mammary gland secretion at 20 mg/kg and above. Dilatation of the lumina and apoptosis of endometrial cells in the uterus, mucinification in the vagina and increase in serum follicle-stimulating hormone were seen with 80 mg/kg. Among the parameters examined in the present experimental system, effects of 17alpha-methyltestosterone on endocrine-related organs were detected in organ weights and histopathological examination of both sexes, and in serum hormones and estrous cycle of females. Based on these results, the no-observed-adverse-effect level (NOAEL) in the present study was estimated to be below 5 mg/kg per day. In particular, effects were most sensitively detected by organ weights and histopathological examination of sexual organs.

Administration, Oral↗

3alpha,5alpha-THP: a potential plasma neurosteroid biomarker in Alzheimer's disease and perhaps non-Alzheimer's dementia.

RATIONALE: A plasma biomarker for neurodegenerative disease is desirable because blood is relatively simple to obtain compared with other biological samples such as cerebrospinal fluid. Recent literature suggests that neurosteroid metabolism may be altered in Alzheimer's disease (AD). OBJECTIVES: We sought to measure the plasma levels of seven steroids to assess their potential as biomarkers for dementia and AD. METHODS: Steroids were measured using validated radioimmunoassay methods in AD (n=15), non-AD dementia (n=4), and control subjects (n=20). Demented subjects were in the mild-to-moderate stages of illness. Measurements were done blind to subject status in an independent laboratory. RESULTS: The notable finding was the significantly lower 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) level in demented subjects compared with controls (25% decrease; p=0.004); 3alpha,5alpha-THP was the only one of the steroids demonstrating an effect of dementia. CONCLUSION: Lowered 3alpha,5alpha-THP levels appear promising as a biomarker in dementia, but further work is needed to establish the sensitivity and specificity of these findings in AD.

Aged↗

A new oral testosterone undecanoate formulation.

Testosterone undecanoate has been available on the market for more than 20 years. This testosterone ester is used worldwide for oral treatment of male hypogonadism. So far, testosterone undecanoate has been dissolved in oleic acid, leading to inconvenient storage conditions. It will now be available in a new formulation with castor oil and propylene glycol laurate instead of oleic acid, thus improving storage conditions markedly (stable at room temperature for approximately 3 years). Pharmacokinetic and pharmacodynamic studies have demonstrated bioequivalence of the old and the new formulation of testosterone undecanoate. Therefore, the results of studies that were performed with the old formulation can be transferred to the clinical use of the new formulation. Controlled studies have shown its efficacy in the treatment of symptoms associated with reduced serum testosterone levels. In these cases testosterone undecanoate improves bone mineral density, quality of life, muscle mass, libido and mood. Further studies will help evaluate the efficacy and safety of the new formulation in the treatment of elderly men with late-onset hypogonadism.

Administration, Oral↗

Treatment of sexual dysfunction of hypogonadal patients with long-acting testosterone undecanoate (Nebido).

Recently, testosterone undecanoate (TU), a new parenteral testosterone (T) preparation has been introduced. Two of its distinctive features are (a) its prolonged action: after two initial loading injections 6 weeks apart, usually only one injection every 12 weeks is needed (b) over the full interval between two injections, plasma T levels are in the physiological range. New research presents convincing evidence that T has profound effects on tissues of the penis involved in the mechanism of erection and that testosterone deficiency impairs the anatomical and physiological substrate of erectile capacity, which is, at least, in part reversible upon androgen therapy. Our studies with TU demonstrated that venous leakage could be corrected with T treatment in a number of patients. We further could show that sexual functions, in a substantial number of elderly men, can be restored with treatment with T only. So, these results argue for determination of T levels in elderly men with sexual problems. If the levels are subnormal, T treatment is warranted.

Aging↗

The expression of androgen receptors in human neck and limb muscles: effects of training and self-administration of androgenic-anabolic steroids.

The purpose of this study was to investigate the immunohistochemical expression of androgen receptors (AR) in human vastus lateralis and trapezius muscles and to determine whether long-term strength training and self-administration of androgenic-anabolic steroids are accompanied by changes in AR content. Biopsy samples were taken from eight high-level power-lifters (P), nine high-level power-lifters who used anabolic steroids (PAS) and six untrained subjects (U). Myonuclei and AR were visualised in cross-sections stained with the monoclonal antibody against AR and 4',6-diamidino-2-phenylindole. The proportion of AR-containing myonuclei per fibre cross-section was higher in the trapezius than in the vastus lateralis (P<0.05). In the trapezius, the proportion of AR-containing myonuclei was higher in P compared to U and in PAS compared to both P and U (P<0. 05). On the contrary, in the vastus lateralis, there were no differences in AR content between the three groups. Myonuclear number in both muscles was higher in P compared to U and in PAS compared to both P and U (P<0.05). In conclusion, AR content differs greatly between human neck and limb muscles. Moreover, the regulation of AR-containing myonuclei following training and self-administration of androgenic-anabolic steroids is muscle dependent.

Adult↗