title: Hedgehog signalling promotes germ cell survival in the rat testis.
abstract: Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell-derived desert hedgehog (DHH) guides the formation of testis cords and differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh signalling pathway components are also expressed in postnatal testis. In the rat testis the transcription factor of the Hh pathway, glioma-associated oncogene homologue (GLI1), is expressed by a wide variety of germ cells. This suggests that Hh signalling is involved in spermatogenesis at many different levels. Our data show that canonical Hh signalling is turned off in early condensing spermatids that strongly express the negative regulator of the pathway, suppressor of fused (SUFU). Most of the Hh pathway specific mRNAs display the highest values in stages II-VI of the rat seminiferous epithelial cycle. The key endocrine regulator of germ cell differentiation, FSH, down-regulates Dhh mRNA levels in vitro. Hh signalling inhibition in vitro leads to massive apoptosis of germ cells. In prepubertal rat testis imatinib mesylate-induced inhibition of tyrosine kinases impinges on Dhh transcript levels and Hh signalling. Our data indicate that Hh signalling is part of the paracrine signalling network in the rat testis. It promotes the survival of germ cells and is suppressed by FSH.
authors: Department of Physiology, University of Turku, FIN-20520 Turku, Finland. juho-antti.makela@utu.fi
authors: Juho-Antti
authors: JA
authors: Mäkelä
authors: Vuokko
authors: V
authors: Saario
authors: Sonia
authors: S
authors: Bourguiba-Hachemi
authors: Mirja
authors: M
authors: Nurmio
authors: Kirsi
authors: K
authors: Jahnukainen
authors: Martti
authors: M
authors: Parvinen
authors: Jorma
authors: J
authors: Toppari
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000068877:Imatinib Mesylate; D008297:Male; D019899:Paracrine Communication / Q000187:drug effects / Q000235:genetics; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013723:Teratogens / Q000494:pharmacology; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology*; D014704:Veratrum Alkaloids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D053823:Hedgehog Proteins; D010879:Piperazines; D011743:Pyrimidines; D013723:Teratogens; D014704:Veratrum Alkaloids; D000068877:Imatinib Mesylate; D005640:Follicle Stimulating Hormone; C000541:cyclopamine