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1. Quantitation of testolactone and 4,5-dihydrotestolactone in plasma and urine using high-performance liquid chromatography

Author

R.V. Clark, Dulal C. Chatterji, R.J. Sherins, Russell L. Yeager, V.L. Pascucci, and Joseph F. Gallelli

Subjects
Male, Time Factors, Chromatography, Metabolite, Coefficient of variation, Testolactone, Extraction (chemistry), General Chemistry, Urine, High-performance liquid chromatography, Absorbance, chemistry.chemical_compound, chemistry, Pharmacokinetics, medicine, Humans, Chromatography, High Pressure Liquid, medicine.drug
Abstract

A rapid, sensitive, and selective assay is described for the quantitation of both testolactone and its recently identified metabolite, 4,5-dihydrotestolactone, in plasma and urine using high-performance liquid chromatography. The procedure includes a methylene chloride extraction prior to chromatography and quantitation using peak height ratios (ultra-violet absorbance detection, 242 nm) of testolactone and 4,5-dihydrotestolactone to the internal standard, testosterone. A sensitivity of 20 ng/ml for both testolactone and 4,5-di-hydrotestolactone is easily achieved using only 0.5 ml of sample. Mean recoveries for testolactone and its metabolite are 95.0% and 81.8%, respectively, and the mean coefficient of variation of the procedure is 3.5% for the drug and 7.1% for the metabolite. This method is currently being used to study the pharmacokinetics of testolactone and 4,5-dihydrotesto-lactone in male patients. A steady-state plasma concentration versus time profile from a representative patient is included.

Published
1983
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2. Evidence for induction of germinal aplasia in male rats by environmental exposure to boron

Author

R.J. Sherins, Robert L. Dixon, and I.P. Lee

Subjects
Male, inorganic chemicals, endocrine system, medicine.medical_specialty, Sorbitol dehydrogenase, Biology, Toxicology, Lesion, chemistry.chemical_compound, Internal medicine, Lactate dehydrogenase, Testis, medicine, Animals, Testosterone, Boron, Epididymis, Pharmacology, Testicular atrophy, Prostate, Proteins, Histology, Environmental exposure, Luteinizing Hormone, medicine.disease, Sertoli cell, Diet, Rats, Fertility, Endocrinology, medicine.anatomical_structure, chemistry, Follicle Stimulating Hormone, medicine.symptom
Abstract

In view of recent reports of adverse effects of environmental boron on testicular function, we have studied some biochemical, morphological, and physiologic aspects of gonadal function in adult male rats exposed to increased levels of dietary boron. The experimental animals were fed 500, 1000, and 2000 ppm of boron added as borax to standard laboratory chow for 30 to 60 days. Fertility, testicular, and epididymal histology; specific activities of testicular and prostatic enzymes; plasma concentrations of FSH, LH, and testosterone, and boron content of plasma and testes were evaluated. Some of the rats treated with the highest dose were followed for up to 1 year following cessation of boron exposure. In both 30- and 60-day feeding studies, male rats receiving 500 ppm suffered no significant adverse effects. In contrast, male rats receiving 1000 and 2000 ppm of boron displayed a significant loss of germinal elements, decrease in seminiferous tubular diameter, and accumulation of testicular boron. The testicular atrophy was greatest at the highest dose, and depletion of germ cells was complete after 60 days of exposure. These morphological changes were associated with reduction of specific activities of hyaluronidase, sorbitol dehydrogenase, and lactate dehydrogenase isozyme-X, markers of postmeiotic germ cells. In contrast, specific enzyme activities of glyceraldehyde 3-phosphate and malate dehydrogenase were significantly elevated above control values, an effect probably of the relative enrichment of Sertoli cells and spermatogonia. The germinal depletion was associated with a significant increase in plasma FSH concentration, a variable increase in plasma LH levels (not significant), and normal concentrations of plasma testosterone. The increased plasma FSH and germinal cell depletion were time- and dose-dependent. Serial mating studies demonstrated reduced fertility without change in copulatory behavior. The duration of reduced fertility was greater at the higher dose and the longer duration of exposure. Germinal aplasia, elevated FSH, and infertility persisted for at least 8 months following cessation of boron exposure at the highest dose. These data suggest that boron accumulation in testes is associated with progressive germ cell depletion and that the testicular lesion can persist long after toxic exposure to boron has occurred. Further long-term studies are necessary to determine whether testicular dysfunctions can occur after prolonged exposure to levels of boron which prevail in some areas of the environment.

Published
1978
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3. LIST OF CONTRIBUTORS AND DISCUSSANTS

Author

J.A. Archer, A. Arimura, G.D. Aurbach, J. Axelrod, R.S. Bar, A. Bartke, D.B. Bartosik, F.C. Bartter, M. Beato, J.C. Beck, N.H. Bell, V. Bennett, L. Birnbaumer, E.M. Bogdanove, B. Boss, R.M. Boyar, E.D. Bransome, P. Brazeau, H.J. Brodie, J.C. Brown, M. Brown, R. Burgus, G.N. Burrow, G.T. Campbell, S. Cataland, Kwen-Jen Chang, L.R. Chase, S.L. Cohen, P. Colman, P.G. Condliffe, B.A. Cross, P. Cuatrecasas, I.J. Davies, P. De Meyts, B.M. Dobyns, M.B. Dratman, M. Drosdonsky, J.R. Dryburgh, J. Dupré, R.E.J. Dyball, R.G. Dyer, P. Feigelson, F. Flores, P. Freychet, H.G. Friesen, J.W. Funder, J.R. Gavin, V.L. Gay, J.M. George, J.R. Gill, S. Glick, I.D. Goldfine, H.M. Goodman, P. Gorden, R.O. Creep, M.A. Greer, R. Guillemin, S.L. Gupta, A. Haksar, S.N.S. Hanjan, G.A. Hedge, L. Hellman, M. Herman, J.M. Hershman, M.D. Hollenberg, R. Jewelewicz, C.W. Jones, C.R. Kahn, M. Kalimi, S. Kapen, F.J. Karsch, A.D. Kenny, L.A. Killewich, J.I. Kitay, E. Knobil, J. Konishi, J. Kowal, D.T. Krieger, R. Krishnaraj, J.P. Kriss, M. Kuhn, N. Kumar, B.L. Lasley, H. Leblanc, R.M. Lequin, M.A. Lesniak, R. Levy, D.W. Lincoln, N. Ling, M.B. Lipsett, S.M. McCann, J.M. McKenzie, G.S. McKnight, W.B. Malarky, B.H. Marks, K. Megyesi, J.C. Melby, C. Monder, J.F. Morris, F. Naftolin, D.M. Neville, M.B. Nikitovitch-Winer, S.J. Nillius, J.M. Nolin, R. Palacios, M.R. Pandian, J.A. Parsons, Z. Petro, B.T. Pickering, B.I. Posner, S. Raiti, J.A. Ramaley, V.V. Reddy, B.F. Rice, C. Rivier, J. Rivier, J.S. Roberts, R. Rolland, A.L. Rosenbloom, S.A. Ross, J. Roth, K.J. Ryan, N. Samaan, R.J. Santen, R.K. Saxena, R.T. Schimke, E. Schonbaum, G. Schutz, N.B. Schwartz, A.A. Shaikh, D.J. Shapiro, R.J. Sherins, T.M. Siler, H.W. Sokol, A.H. Soil, K. Sterling, D. Sulhvan, D. Sunde, Y. Takaoka, G.P. Talwar, T.C. Theoharides, J.L. Vaitukaitis, W. Vale, H. Valtin, W.P. Vander Laan, C.A. Villee, C.F. Wang, R.F. Weick, J. Weisz, E.D. Weitzman, A. White, R.J. White, L. Wolin, and S.S.C. Yen

Published
1975
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4. LIST OF CONTRIBUTORS AND DISCUSSANTS

Author

M.S. Aiyer, A. Albert, R.W. Alexander, H.J. Anderson, M. Aubert, G.D. Aurbach, H.W.G. Baker, C.W. Bardin, A. Bartke, F.C. Bartter, P.H. Bennett, R.S. Bernstein, L. Bitensky, R. Boucher, H. Bourne, G.D. Braunstein, E.L. Bravo, W.J. Bremner, E.M. Brown, L.L. Brunton, H.G. Burger, G.N. Burrow, G.T. Campbell, M.G. Caron, A.C. Carter, R.T. Chatterton, J. Chayen, P. Coffino, S.L. Cohen, G. Constantopoulos, J.R. Daly, D.M. de Kretser, M. DiGirolamo, W.H. Dillmann, O.V. Dominguez, W.L. Duax, A. Dulmanis, J.M. Earll, L.W. Eddie, I.S. Edelman, R.A. Edgren, C. Faiman, J.L. Fakunding, U. Friedrich, H.G. Friesen, R.E. Frisch, L.A. Frohman, J. Furth, D. Ganten, J.D. Gardner, U. Gehring, J. Geller, R. Gendrich, J. Genest, J.M. George, J.R. Gill, A.G. Gilman, H.M. Goodman, G. Gross, M. Grumbach, W. Hembree, J. Hochman, C. Huckins, B. Hudson, P.A. Insel, L.S. Jacobs, R. Jewelewicz, S. Kaplan, T. Kennedy, A.D. Kenny, E.J. Keogh, M.A. Kirschner, E. Knobil, D. Koerner, J. Kowal, D.T. Krieger, O. Kuchel, H.E. Kulin, P.M. LeCompte, V.W.K. Lee, R.J. Lefkowitz, I. Lemaire, R.M. Lequin, L.E. Limbird, Y.C. Lin, H.R. Lindner, M.B. Lipsett, B. Little, N. Loveridge, J.W. McArthur, J.M. McKenzie, M.E. Maguire, J.B. Martin, A.R. Means, J.C. Melby, K.L. Melmon, F. Messerli, J.V. Mickey, M. Miller, E. Montoya, C. Mukherjee, B.E.P. Murphy, F. Naftolin, G.D. Niswender, W. Nowaczynski, A. Nureddin, W.D. Odell, J.T. Oliver, J.H. Oppenheimer, J.L.H. O'Riordan, J. Orr, R. Osathanondh, H. Papkoff, J.A. Parsons, J.R. Pasqualini, C.A. Paulsen, W.H. Pearlman, O.H. Pearson, F.G. Perón, N.P. Plotnikoff, S. Raiti, J.A. Ramaley, P.L. Rayford, L. Renaud, G.C. Rennie, B.F. Rice, D. Rodbard, C.H. Rodgers, D.C. Rohrer, J.M. Rojo-Ortega, E. Rosemberg, U. Rosenqvist, G.T. Ross, N.B. Rushford, R.J. Ryan, M. Saffran, M.R. Sairam, H.H. Samuels, R.J. Santen, H.L. Schwartz, N.B. Schwartz, A. Segaloff, R.J. Sherins, M.R. Sherman, C.H. Sibley, A.M. Spiegel, M.R. Stampfer, B.G. Steinetz, K. Sterling, M.I. Surks, R.S. Swerdloff, N.I. Swislocki, R. Tate, D.J. Tindall, G.S. Tomkins, J.L. Vaitukaitis, P.M. Van Arsdale, R. Vitale, W. Waldhäusl, C.M. Weeks, J. Weisz, W.F. White, R.A. Wiklund, J.F. Wilber, L.T. Williams, J. Winter, and K.R. Yamamoto

Published
1976
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