Steroid biosynthesis

About: Steroid biosynthesis is a research topic. Over the lifetime, 1721 publications have been published within this topic receiving 58977 citations.

Frequent association of alternative splicing of NER, a nuclear hormone receptor gene in cancer tissues

Abstract: We have detected frequent alternative splicing of a gene that encodes NER, a protein homologous to the retinoic acid receptors, in cancer cells. Western and immunohistochemical analyses disclosed accumulation of a large amount of the aberrant NER product, generated by alternative splicing that caused skipping of an exon corresponding to the DNA-binding domain, in the nucleoli of cells of cancer cell lines and primary cancer tissues. The aberrant protein was detected in 116 of 228 primary cancers developed in various tissues including breast and colon, but was absent in the corresponding normal tissues; it was also detected in 31 of 39 cancer cell lines. This observation may imply that the aberrant NER product has some relation to the development and/or progression of cancers in a variety of human tissues.

Aromatase inhibition and inactivation.

Abstract: Aromatase is the key enzyme in the synthesis of estrogens and mediates the conversion of androstenedione and testosterone to estrone and estradiol. Because of the importance of estrogen in stimulating breast cancers, the inhibition of estrogen synthesis is a logical approach to treatment. Aromatase is an excellent target for inhibition, because it is the last step in steroid biosynthesis, and, therefore, there are no important downstream enzymes to be affected. In addition, although aromatase is a P-450 enzyme and shares common features with other enzymes in this class, such as liver metabolizing enzymes and steroidogenic enzymes, it has unique features in the aromatizing reaction, features that are amenable to the development of selective inhibition. The approach we took to develop the first aromatase inhibitors was to design substrate analogues based on the structure of androstenedione. Some of these inhibitors, such as 4-hydroxyandrostenedione [4-OHA (later known as formestane)], also cause enzyme inactivation. Instead of being released at the end of the reaction, the substrate analogue remains bound. Therefore, the inhibitor is not required to be present at all times to maintain inhibition, and it has high enzyme specificity. Subsequently, other investigators have taken a different approach to developing compounds based on inhibitors of P-450 enzymes. High selectivity has been achieved with some of these reversible inhibitors. We have developed a unique animal model with human tumors to compare the antitumor efficacy of antiestrogens and aromatase inhibitors and to optimize their use in sequence and combination as a guide for future clinical trials.

Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells.

Abstract: Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis.