Track topics on Twitter Track topics that are important to you
The study reveal a previously unknown pathway of masculinisation of the external genitals, and may explain why placental dysfunction is associated with disorders of male genital development.
The findings by Paul Fowler of the University of Aberdeen, Michelle Bellingham of the University of Glasgow and colleagues in the UK, France and Sweden have been published in open-access journal PLOS Biology.
During development of the male foetus, the testes release testosterone, a steroid hormone which is converted to 5α-dihydrotestosterone (DHT) by the genital tubercle, helping to ensure that this primordial structure develops into a penis, rather than into the female clitoris. Recently, penis development was shown to also depend on a second process, called the alternative or ‘backdoor’ pathway, which also ends in the production of DHT but doesn’t depend on the production of testosterone by the testes. However, the details of this backdoor pathway, including the source of the DHT precursor, have been unclear.
To learn more about this pathway, the authors used mass spectrometry to measure levels of different steroids in foetal plasma and tissue during the second trimester, when the most critical steps in penis development occur. They also analysed gene expression levels in various tissues of key enzymes known to be involved in hormone synthesis.
They found that androsterone, a steroid from the backdoor pathway which can be converted to DHT, was the principal androgen in the male foetal circulation, and that levels of both androsterone and testosterone were lower in the female foetal circulation. They also found that enzymes needed for the backdoor pathway were present primarily in non-gonadal tissue, including the liver and the placenta.
Since androsterone can be made from progesterone, the authors suggest that placental progesterone or related compounds are the likely source of androsterone in the backdoor pathway. While it remains unclear why a sex difference in foetal androsterone levels exists, the authors found high expression in the male genital tubercle of enzymes required to convert androsterone to DHT. The male genital tubercle appears, therefore, to be able to convert both testosterone and androsterone into DHT.
“Our results demonstrate that masculinisation of the male foetus depends not only on the testes, but also on other tissues, especially the placenta,” said Fowler and Bellingham. “They also suggest an explanation for why disorders of placental insufficiency can lead to hypospadias and other abnormalities of growth of the male external genitalia.”
Original Article: Development of male genitals in womb requires more than testesNEXT ARTICLE
Diabetes Diabetes Endocrine Disorders Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several g...
Endocrine disorders are grouped into two categories: hormone imbalance - when a gland produces too much or too little of an endocrine hormone development of lesions (such as nodules or tumors) in the endocrine system, which may or may not affect...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...