{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T18:40:12Z","timestamp":1698604812111},"reference-count":51,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To further investigate the regulatory mechanisms responsible for the control of testicular inhibin\/activin subunit gene expression, inhibin-\u03b1, -\u03b2A, and -\u03b2B messenger RNA (mRNA) levels were assessed after ethylene dimethane sulfonate (EDS)-induced destruction of Leydig cells (LC) in different animal models: the intact rat, the rat treated with high doses of testosterone, and the unilaterally cryptorchid rat. In intact rats, EDS selectively eliminates the mature adult-type LCs, activating the proliferation and differentiation of preexisting LC precursors into a new population of functionally active LCs. In this model, a single dose of EDS (75 mg\/kg BW, ip) induced a significant increase in testicular inhibin-\u03b1 and -\u03b2B mRNA levels 5 days after treatment (5.0- and 5.5-fold increases, respectively), whereas inhibin-\u03b2A mRNA remained undetectable upon Northern hybridization in control and EDS-treated testes. Moreover, in situ hybridization analysis demonstrated that the increased expression of inhibin-\u03b1 and -\u03b2B mRNAs observed 5 days after EDS takes place mainly in Sertoli cells. Along with LC repopulation, the expression level of inhibin-\u03b1 and -\u03b2B messages declined, and inhibin-\u03b1 mRNA returned to control values on day 40 after EDS. This treatment, however, failed to alter the pattern of testicular expression of FSH receptor and androgen-binding protein mRNAs, thus suggesting selectivity for the above effects. In EDS-treated rats supplemented with high doses of testosterone, the preexisting mature LCs are destroyed, but, due to elevated testosterone concentrations, disruption of spermatogenesis is attenuated, and the post-EDS rise in serum gonadotropins is blocked; the latter prevents LC regeneration. In this model, a 5.0-fold increase in inhibin-\u03b1 mRNA levels, similar to that found in intact animals, was detected 5 days after EDS administration, but the rise in inhibin-\u03b2B levels was partially delayed. In addition, the blockade of LC repopulation resulted in permanent elevation of inhibin-\u03b1 and -\u03b2B messages throughout the study period. In unilaterally cryptorchid rats, the abdominal testis shows disrupted spermatogenesis and altered paracrine environment that expedites LC repopulation after EDS treatment. In this model, the abdominal testes showed a significant 2.5-fold increase in inhibin-\u03b1 mRNA levels 5 days after EDS, but no effect was found in those of inhibin-\u03b2B. Further, the faster rate of LC repopulation resulted in precocious decline of inhibin-\u03b1 mRNA levels. Finally, the expression of inhibin\/activin subunit mRNAs was monitored during postnatal testicular development, specifically at the time of regression of fetal-type LCs and appearance of those of the adult type. High levels of expression of inhibin-\u03b1 and -\u03b2B mRNAs were detected in neonatal and infantile testes. A sharp decline in both messages took place between days 15\u201320, i.e. at the time when fetal-type Leydig cells are replaced by adult-type cells. From this time point onward, inhibin-\u03b1 and -\u03b2B mRNA levels remained low, ranging between 15\u201330% of the maximum. In conclusion, our results suggest that the adult-type LCs differentially modulate the expression of inhibin\/activin subunit genes and point to a major inhibitory role in this cell type on expression of the inhibin-\u03b1 gene.<\/jats:p>","DOI":"10.1210\/endo.140.12.7193","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T16:10:10Z","timestamp":1389197410000},"page":"5761-5770","source":"Crossref","is-referenced-by-count":7,"title":["The Pattern of Inhibin\/Activin \u03b1- and\u03b2B-Subunit Messenger Ribonucleic Acid Expression in Rat Testis after Selective Leydig Cell Destruction by Ethylene Dimethane Sulfonate1"],"prefix":"10.1210","volume":"140","author":[{"given":"Manuel","family":"Tena-Sempere","sequence":"first","affiliation":[{"name":"Departments of Physiology (M.T.-S., J.K., A.R., W.Y., I.H.), University of Turku, 20520 Turku, 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Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilpo","family":"Huhtaniemi","sequence":"additional","affiliation":[{"name":"Departments of Physiology (M.T.-S., J.K., A.R., W.Y., I.H.), University of Turku, 20520 Turku, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071619405380100_R1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1146\/annurev.cb.06.110190.003121","article-title":"The transforming growth factor-\u03b2 family.","volume":"6","author":"Massague\u0301","year":"1990","journal-title":"Annu Rev Cell Biol"},{"key":"2020071619405380100_R2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1038\/318659a0","article-title":"Complementary DNA sequences of ovarian follicular fluid inhibin show precursor structure and homology with transforming growth 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