PMID- 21893610 OWN - NLM STAT- MEDLINE DCOM- 20120319 LR - 20211020 IS - 1741-7899 (Electronic) IS - 1470-1626 (Print) IS - 1470-1626 (Linking) VI - 142 IP - 5 DP - 2011 Nov TI - Hedgehog signalling promotes germ cell survival in the rat testis. PG - 711-21 LID - 10.1530/REP-11-0110 [doi] AB - 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. FAU - Makela, Juho-Antti AU - Makela JA AD - Department of Physiology, University of Turku, FIN-20520 Turku, Finland. juho-antti.makela@utu.fi FAU - Saario, Vuokko AU - Saario V FAU - Bourguiba-Hachemi, Sonia AU - Bourguiba-Hachemi S FAU - Nurmio, Mirja AU - Nurmio M FAU - Jahnukainen, Kirsi AU - Jahnukainen K FAU - Parvinen, Martti AU - Parvinen M FAU - Toppari, Jorma AU - Toppari J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110905 PL - England TA - Reproduction JT - Reproduction (Cambridge, England) JID - 100966036 RN - 0 (Antineoplastic Agents) RN - 0 (Benzamides) RN - 0 (Hedgehog Proteins) RN - 0 (Piperazines) RN - 0 (Pyrimidines) RN - 0 (Teratogens) RN - 0 (Veratrum Alkaloids) RN - 8A1O1M485B (Imatinib Mesylate) RN - 9002-68-0 (Follicle Stimulating Hormone) RN - ZH658AJ192 (cyclopamine) SB - IM MH - Animals MH - Animals, Newborn MH - Antineoplastic Agents/pharmacology MH - Benzamides MH - Cell Survival/drug effects/genetics MH - Follicle Stimulating Hormone/pharmacology MH - Gene Expression Regulation, Developmental/drug effects MH - Germ Cells/drug effects/metabolism/*physiology MH - Hedgehog Proteins/antagonists & inhibitors/genetics/metabolism/*physiology MH - Imatinib Mesylate MH - Male MH - Paracrine Communication/drug effects/genetics MH - Piperazines/pharmacology MH - Pyrimidines/pharmacology MH - Rats MH - Rats, Sprague-Dawley MH - Sexual Maturation/drug effects/genetics/physiology MH - Signal Transduction/drug effects/genetics/physiology MH - Teratogens/pharmacology MH - Testis/cytology/growth & development/*metabolism/*physiology MH - Veratrum Alkaloids/pharmacology PMC - PMC3207727 EDAT- 2011/09/07 06:00 MHDA- 2012/03/20 06:00 PMCR- 2011/11/01 CRDT- 2011/09/07 06:00 PHST- 2011/09/07 06:00 [entrez] PHST- 2011/09/07 06:00 [pubmed] PHST- 2012/03/20 06:00 [medline] PHST- 2011/11/01 00:00 [pmc-release] AID - REP-11-0110 [pii] AID - REP110110 [pii] AID - 10.1530/REP-11-0110 [doi] PST - ppublish SO - Reproduction. 2011 Nov;142(5):711-21. doi: 10.1530/REP-11-0110. Epub 2011 Sep 5.