Regulation der Keimdrüsenfunktion des Mannes

In diesem Schwerpunkt werden die endokrine Steuerung der Hodenfunktion durch das Hypopysen-Hypothalamus-System, die parakrine/autokrine Regulation der Keimzellproduktion (lokale testikuläre Faktoren und Interaktionen) sowie die Funktion von keimzellspezifischen Genen untersucht. Die molekulare Wirkung des Follikel-Stimulierenden Hormons (FSH) in Sertoli-Zellen konnte durch die Erstellung von Genexpressionsprofilen mittels cDNA-Arrays erstmals charakterisiert werden. Damit kann die Bedeutung von FSH für die Spermatogenese besser verstanden werden. Für diese Arbeiten wurde Dr. Kai Strothmann mit dem Marius-Tausk-Förderungspreis der Deutschen Gesellschaft für Endokrinologie ausgezeichnet. Wir konnten zeigen, daß die Anzahl der Spermien abhängig ist von der Anzahl eines repetitiven Elements im Androgenrezeptor, den sogenannten CAG-Repeats. Die Spermienzahl nimmt bei einer größeren Anzahl von CAG-Repeats ab. Damit wurde erstmals ein genetischer Faktor für die Effizienz der Spermatogenese beim Menschen identifiziert. Der Transkriptionsfaktor CREM spielt eine entscheidende Rolle bei der Reifung der Spermien.

Drittmittelgeber:

Deutsche Forschungsgemeinschaft, Fritz-Thyssen-Stiftung

Beteiligte Wissenschaftler:

Dr. Collin Blume, Dr. Martin Brinkworth, PD Dr. Jörg Gromoll, Dr. Michael Kuhlmann, Prof. Dr. Eberhard Nieschlag, Prof. Dr. Manuela Simoni, PD Dr. Stefan Schlatt, Dr. Kai Strothmann, Prof. Dr. Gerhard Weinbauer, Dipl. Biol. Viktoria von Schönfeldt

Veröffentlichungen:

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Anderson, D., P.C. Jenkinson, A.J. Edwards, J.A. Hughes, M.H. Brinkworth: Commentary: Paternal legacies. Teratogenesis, Carconogenesis, Mutagenesis 19, 105-108 (1999)

Strothmann, K., J. Gromoll: DNA-Array-Technologie: Ein Meilenstein in der molekularen Endokrinologie. Endokrinologie Informationen 1/99:19-23 (1999)

Behr, R., G.F. Weinbauer: Germ cell-specific CREM expression in rodent and primate testis is maintained despite gonadotropin deficiency. Endocrinol. 14, 2746-2754 (1999)

Edwards, Anne J., D. Anderson, M.H. Brinkworth, B. Myers, J.M. Parry: An investigation of male-mediated F1 effects in mice treated acutely and sub-chronically with urethane. Teratogenesis, Carcinogenesis, Mutagenesis 19, 87-103 (1999)

Anderson, D., A. Yardley-Jones, T.-W. Yu, J.A. Hughes, M.H. Brinkworth: Modulation of ras p21 oncoprotein levels and DNA strand breakage in human cells with chemotherapeutic agents and/or deferoxamine. Teratogenesis, Carcinogenesis and Mutagenesis 18, 219-230 (1999)

von Schönfeldt, V., H. Krishnamurthy, L. Foppiani, St. Schlatt: Magnetic cell sorting is a fast and effective method of enriching viable spermatogonia from Djungarian hamster, mouse and marmoset monkey testes. Biol. Reprod. 61, 582-589 (1999)

Simoni, M., V. Rochira, M. Faustini Fustini, C. Carani: Estrogen resistance and aromatase deficiency. In: "Regulation of Pituitary Hormone Secretion", Proceedings of the HypoCCS Symposium on "Regulation of Pituitary Hormone Secretion", 1999

Weinbauer, G.F., J. Wessels: "Paracrine" control of spermatogenesis. Andrologia 31, 249-262 (1999)

Schlatt, S., Y. Zhengwei, T. Meehan, D.M. de Kretser, K. Lakoski Loveland: Application of morphometric techniques to postnatal rat testes in organ culture: insights into testis growth. Cell Tissue Res 298, 335-343 (1999)

Schmidt, A., J. Gromoll, G.F. Weinbauer, H.-J. Galla, S. Chappel, M. Simoni: Cloning and expression of cynomolgus monkey (Macaca fascicularis) gonadotropins luteinizing hormone and follicle-stimulating hormone and identification of two polymorphic sites in the luteinizing hormone b subunit. Mol. Cell. Endocrinol. 156, 73-83 (1999)

Armour, J.A.L., M.H. Brinkworth, A. Kamischke: Direct analysis by small-pool PCR of MS205 minisatellite mutation rates in sperm after mutagenic therapies. Mut. Res. 15:73-80 (1999)

Conway, G.S., E. Conway, C. Walker, W. Höppner, J. Gromoll, M. Simoni: Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome. Clin. Endocrinol. 51, 97-99 (1999)

Behr, R., N. Hunt, R. Ivell, J. Wessels, G.F. Weinbauer: Cloning and expression analysis of testis-specific cAMP responsive element modulator (CREM) activators in the nonhuman primate (Macaca fascicularis): comparison with other primate and rodent species. Biol. Reprod. 62, 1344-1345 (2000)

Brendel, H., M. Niehaus, A. Lerchl: Direct suppressive effects of weak magnetic fields (50 Hz and 162/3 Hz) on melatonin synthesis in the pineal gland of Djungarian hamsters (Phodopus sungorus). J Pineal Res. 29, 228-233 (2000)

Pusch, W., M. Balvers, G. F. Weinbauer, R. Ivell: The rat endozepine-like peptide (ELP) gene is highly expressed in late haploid stages of male germ cell development. Biol. Reprod. 63, 763-768 (2000)

Gromoll, J., M. Bröcker, M. Derwahl, W. Höppner: Detection of mutations in glycoprotein hormone receptors.Methods 21, 83-97 (2000)

Weinbauer, G.F., H. Aslam, H. Krishnamurthy, M.H. Brinkworth, A. Einspanier, J.K. Hodges: Quantitative analysis of spermatogenesis and apoptosis in the common marmoset (Callithrix jacchus) reveals high spermatogonial turnover and spermatogenic efficiency. Biol. Reproduc., 64,120-126 (2001)

Behr, R., G.F. Weinbauer: CREM activator and repressor isoforms in human testis: sequence variations and inaccurate splicing during impaired spermatogenesis. Mol Hum Reprod 6, 967-972, (2000)

Schlatt, S., V. v. Schönfeldt, A.G. Schepers: Male germ cell transplantation: an experimental approach with a clinical perspective. Br. Med. Bulletin, 12.7.2000 (in press)

Valentin M., M. Balvers, W. Pusch, G.F.Weinbauer, J. Knudsen, R. Ivell: Structure and expression of the mouse gene encoding the endozepine-like peptide from haploid male germ cells. Eur. J. Biochem, 267, 5438-5449 (2000)

Millar, M.M., R.M.Sharpe, G.F.Weinbauer, H.M.Fraser, P.T.K.Saunders.: Marmoset spermatogenesis: organizational similarities to the human. Itn. J of Androl, 23, 266-277 (2000)

Strothmann, K.: Gen-Chips: eine Einführung in die Technologie der modernen Genexpressionsanalyse. Pharmazie in unserer Zeit, 29,303-308 (2000)

Grossmann, B., G. Weinbauer, P. Hirschmann, P.H. Vogel: Conservation of the deleted-in-azoospermia-like-1 (DAZL1) gene structure in old world monkeys points to a homolgous function of DAZL1 in this primate class. Journal of Endocrinology Investigation 23, 616-622, 2000

Weinbauer, G.F., Cooper, T.G.: Assessment of male fertility impairment. In: Towards New Horizons in Primate Toxicology, (ed. R. Korte, G. F. Weinbauer), pp. 13-42. Waxman, Münster (2000)

Simoni, M., J. Gromoll, W. Höppner, A. Kamischke, T. Krafft, D. Stähle, E. Nieschlag: Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J. Clin. Endocr. Metab. 84, 751-755 (1999)

Aslam, H., G. Rosiepen, H. Krishnamurthy, M. Arslan, G. Clemen, E. Nieschlag, G.F. Weinbauer: The cycle duration of the seminiferous epithelium remains unaltered during gonadotropin-releasing hormone (GnRH) antagonist-induced testicular involution in rats and monkeys. J. Endocrinol. 161, 281-288 (1999)

Kamischke, A., E. Nieschlag: Analysis of medical treatment of male infertility. Hum. Reprod. 14, (suppl. 1) 1-23 (1999)

Sjögren, I., S. Ekvärn, U. Zühlke, F. Vogel, W. Bee, G.F. Weinbauer, E. Nieschlag: Lack of effects of recombinant human GH on spermatogenesis in the adult cynomolgus monkey (Macaca fascicularis). Eur. J. Endocrinol. 140, 350-357 (1999)

Kamischke, A., G.F. Weinbauer, A. Semjonow, A. Lerchl, K-D. Richter, E. Nieschlag: Estradiol and high dose dihydrotestosterone treatment causes identical changes in cynomolgus monkey prostate volume and histology to those caused by testosterone alone. J. Androl. 20, 601-610 (1999)

Foppiani, L., S. Schlatt, M. Simoni, G.F. Weinbauer, U. Hacker-Klom, E. Nieschlag: Inhibin B is a more sensitive marker of spermatogenetic damage than FSH in the irradiated non-human primate model. J. Endocrinol. 162, 393-400 (1999)

Gromoll, J., G.F. Weinbauer, H. Skaletsky, S. Schlatt, M. Rocchietti-March, D.C. Page, E. Nieschlag: The Old World monkey DAZ (Deleted in Azoospermia) gene yields insights into evolution of the DAZ gene cluster on humane Y chromosome. Hum. Mol. Genet. 8, 2017-2024 (1999)

Brinkworth, M.H., E. Nieschlag: Association of cyclophosphamide-induced male-mediated, foetal abnormalities with reduced paternal germ-cell apoptosis. Mut. Res. 447, 149-154 (2000)

Rocchietti-March, M., G.F. Weinbauer, D.C. Page, E. Nieschlag, J. Gromoll: Dazl protein expression in adult rat testis is up-regulated at meiosis and not hormonally regulated. Int. J. Androl. 23, 51-56 (2000)

Perez Mayorga, M., J. Gromoll, H.M. Behre, C. Gassner, E. Nieschlag, M. Simoni: Ovarian response to follicle-stimulating hormone (FSH)stimulation depends on the FSH receptor genotype. J. Clin. Endocr. Metab. 85, No. 9 3365-3369 (2000)