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Developmental expression of testis messenger ribonucleic acids in the rat following propylthiouracil-induced neonatal
1Department of Veterinary Biosciences, University of Illinois, Urbana 61801.
Insights
Propylthiouracil (PTU) causes neonatal hypothyroidism, prolonging Sertoli cell proliferation and delaying testis maturation. Thyroid hormone replacement normalized gene expression, suggesting its direct role in regulating Sertoli cell development.
Area of Science:
- Reproductive Biology
- Endocrinology
- Developmental Biology
Background:
- Neonatal hypothyroidism induced by propylthiouracil (PTU) leads to increased adult rat testis weight.
- This effect is linked to the prolonged proliferation of Sertoli cells.
Purpose of the Study:
- To investigate the developmental effects of PTU on rat testis gene expression.
- To understand the role of thyroid hormone in Sertoli cell development and maturation.
Main Methods:
- Northern analysis was used to examine Sertoli cell mRNA expression in postnatal rat testes.
- Rats were treated with PTU from birth to Day 25, with some receiving thyroid hormone replacement.
Main Results:
- PTU-treated rats showed prolonged expression of genes like Müllerian inhibiting substance (MIS) and c-erbA alpha (thyroid hormone receptor).
- Expression of other Sertoli cell genes (e.g., androgen-binding protein [ABP], clusterin, inhibin-beta B) and a spermatid-specific mRNA (hemiferrin) was delayed.
- Thyroid hormone replacement normalized MIS and c-erbA alpha mRNA levels.
Conclusions:
- Neonatal hypothyroidism alters the developmental expression of key Sertoli cell genes, indicating prolonged mitogenesis and delayed maturation.
- Thyroid hormone may directly influence molecular events that halt Sertoli cell proliferation and promote maturation during early testicular development.
Abstract:
Propylthiouracil- (PTU) induced transient neonatal hypothyroidism increases adult rat testis weight 80-100%; this effect involves prolongation of Sertoli cell proliferation. To gain insight into developmental effects of PTU on the testis, we used Northern analysis to examine chronological expression of Sertoli cell mRNA in postnatal rat testes from rats that were untreated (controls) or were given PTU from birth to Day 25. Treated rats showed prolonged early expression of genes associated with dividing Sertoli cells such as MIS (Müllerian inhibiting substance) and c-erbA alpha (thyroid hormone receptor). Expression of several other Sertoli cell mRNAs (androgen-binding protein [ABP], clusterin, and inhibin-beta B) was delayed, as was that of hemiferrin, a spermatid-specific mRNA. Temporal expression patterns for other mRNAs (sulfated glycoprotein [SGP]-1, transferrin, and inhibin-alpha) were similar in control and treated animals. Additionally, thyroid hormone replacement in PTU-treated animals decreased MIS and c-erbA alpha mRNA expression to control levels. The altered developmental pattern of expression of a number of major Sertoli cell genes reflects a prolonged mitogenesis and delayed maturation of Sertoli cells in neonatally hypothyroid animals. Furthermore, our results suggest that thyroid hormone may directly potentiate molecular events associated with cessation of Sertoli cell proliferation and maturation during early testis development.