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Pharmacogenetics. 2002 Jun;12(4):307-12.
5alpha-reductase 2 polymorphisms as risk factors in prostate cancer.

Soderstrom T, Wadelius M, Andersson SO, Johansson JE, Johansson S, Granath F, Rane A.

Department of Medical Sciences, Clinical Pharmacology, University Hospital, S-751 85 Uppsala, Sweden. torbjorn.soderstromk.ck.lul.se

Prostate cancer is a significant cause of death in Western countries and is under the strong influence of androgens. The steroid 5alpha-reductase 2 catalyzes the metabolism of testosterone into the more potent androgen dihydrotestosterone in the prostate gland. The enzyme is a target in pharmacological treatment of benign prostatic hyperplasia using specific inhibitors such as finasteride. Makridakis et al. have characterized the V89L and A49T polymorphisms in recombinant expression systems. The L allelic variant has a lower Vmax/Km ratio than the V variant. In the A49T polymorphism, the T variant has an increased Vmax/Km ratio. We performed a population-based case-control study of the impact of the SRD5A2 V89L and A49T polymorphisms on the risk of prostate cancer. We also studied the relation between the genotypes and age at diagnosis, tumor, node, metastasis stage, differentiation grade, prostate specific antigen and heredity. The study included 175 prostate cancer patients and 159 healthy controls that were matched for age. There was an association with SRD5A2 V89L LL genotype and metastases at the time of diagnosis, OR 5.67 (95% CI 1.44-22.30) when adjusted for age, differentiation grade, T-stage and prostate specific antigen. Heterozygous prostate cancer cases that carried the SRD5A2 A49T AT genotype were significantly younger than cases that carried the AA genotype, (mean age 66 years vs 71, P = 0.038). The SRD5A2 V89L and A49T polymorphisms were, however, not associated with altered prostate cancer risk. Further studies of the V89L polymorphism may lead to better understanding of the etiology of prostate cancer metastases.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12042668&dopt=Abstract

Ophthalmologe. 2002 May;99(5):380-3.
[Psoriasis and hypogonadism in chronic blepharokeratoconjunctivitis. A case report]

[Article in German]

Horwath-Winter J, Flogel I, Ramschak-Schwarzer S, Hofer A, Kroisel PM.

Universitats-Augenklinik, Auenbruggerplatz 4, 8036 Graz, Osterreich. jutta.horwatfunigraz.ac.at

BACKGROUND: Ocular symptoms occur in approximately 10% of patients with psoriasis vulgaris. PATIENT: We report the clinical course of a 35-year-old male patient with obstructive meibomian gland dysfunction, keratoconjunctivitis and reduced reflex secretion of both eyes. Psoriasis vulgaris and hypothalamic hypogonadism were also present. Genetic testing (cytogenetic and DNA analysis) was performed because of additional facial dysmorphia, brachydactylia and obesity. No chromosomal anomaly was found and no genetic syndrome has yet been diagnosed. The therapeutic regimen included preservative-free artificial tears, occlusion of the puncta and a systemic dose of doxycycline. Dermatological symptoms were treated topically and the hypogonadism was treated with intramuscular injections of testosterone. CONCLUSION: Lacrimal and meibomian glands are influenced by androgens. Therefore hormonal dysfunction can also have contributed to the blepharokeratoconjunctivitis in this patient.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12043294&dopt=Abstract

Wiad Lek. 2002;55(1-2):125-30.
[A case of postmenopausal hyperandrogenism caused by a lipid cell tumor]

[Article in Polish]

Witek A, Skalba P, Chelmicki Z, Pajak J.

Katedry i Kliniki Endokrynologii Ginekologicznej, Slaskiej Akademii Medycznej w Katowicach.

Steroid-secreting neoplasms of the ovary and adrenal gland comprise a small group of tumors. A 76-year-old woman presented hair loss, facial hirsutism associated with increased serum total testosterone level. The adrenal glands and the ovaries were normal on radiological and ultrasonographic investigation. The patient was submitted to a pelvic exploratory laparotomy. Hysterectomy and salpingo-oophorectomy were performed. A solid and circumscribed ovarian tumor of 2 cm in diameter was found. The pathological diagnosis was lipid cell tumor with stromal hyperplasia. The purpose of this report is to relate how difficult is to establish the diagnosis and the origin of the hyperandrogenism in a patient with normal image studies.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12043310&dopt=Abstract

Neuroscience. 2002;112(2):391-8.
Maturational and maintenance effects of testosterone on terminal axon density and neuropeptide expression in the rat vas deferens.

Keast JR, Gleeson RJ, Shulkes A, Morris MJ.

Prince of Wales Medical Research Institute, University of New South Wales, Randwick, Sydney, NSW, Australia. j.keasnsw.edu.au

Testosterone causes growth of many pelvic ganglion cells at puberty and their maintenance during adulthood. Here we have focused on two populations of pelvic ganglion cells that project to the rat vas deferens: noradrenergic neurons that innervate the smooth muscle and synthesize neuropeptide Y, and cholinergic neurons that primarily innervate the mucosa and contain vasoactive intestinal peptide. We have assessed the muscle innervation after pre- or postpubertal castration, using immunohistochemistry to determine axon density and radioimmunoassay to quantify levels of neuropeptides in tissue extracts.Our results show that androgen deprivation in each period causes substantial effects. Noradrenergic axons in the muscle increase in density after castration, partly due to organ size being smaller than age-matched controls. However, when corrected for target size, there is an overall decrease in total number of axons. This implies that androgen exposure at puberty has a direct effect on neurons to ensure that the adult pattern of innervation is attained, and that this is not simply by matching terminal field to target size. Similar effects of pre- and postpubertal castration imply that continued exposure to testosterone is necessary to maintain normal target innervation. Castration in both time periods increased the density of axons containing vasoactive intestinal peptide, however the effects of castration on the total number of these axons in the muscle were more variable. The concentration of vasoactive intestinal peptide increased substantially following either pre- or postpubertal castration although absolute amounts per vas deferens were decreased. Effects on neuropeptide Y concentration were less pronounced but the total amount per vas deferens was decreased after pre- or postpubertal castration.Our study shows that the action of testosterone (or a metabolite) on a pelvic ganglion cell soma is likely to reflect a change in its terminal field, but that these effects are not mediated simply by testosterone influencing the size of its target organ.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12044456&dopt=Abstract

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