By Lee B. Smith, Rod T. Mitchell, Iain J. McEwan
This quantity offers a short résumé of the heritage of testosterone examine, from the early pioneers via to the latest advances within the box. we find how steroid hormones have been first pointed out and the way testosterone used to be proven to be crucial for male improvement. relocating ahead we discover how and the place testosterone is produced, and the way the physique controls testosterone creation. We then examine the effect testosterone has on assorted physique platforms either in the course of their improvement and serve as, and the way perturbation of testosterone motion is linked to ailment. We entire our tale with an exploration of the rising roles of testosterone in scientific treatment, and the long run power for manipulation of the testosterone signaling process for human well-being gain.
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Extra resources for Testosterone: From Basic Research to Clinical Applications
Sample text
The SHBG receptor, although not cloned, is thought to be a G-coupled receptor which signals through adenylate cyclase to raise intracellular cAMP levels, which can then activate the protein kinase A (PKA) pathway (Fig. 3) (Rosner et al. 2010). Rapid signaling by testosterone can also involve an influx of Ca2+-ions, which appears to require signaling from a G-coupled receptor protein to Ca channels. Interestingly, this action also required the classical AR, as demonstrated by the use of antiandrogens (Fix et al.
2009), specific deletion of a gene in just one tissue or cell-type has become a reality. The principle underpinning the Cre/Lox system relies upon the ability of Cre Recombinase to identify, bind and recombine DNA between two LoxP [Locus Of crossing (X-ing) over in P1] sites, each of these 34 bp target DNA sequences consists of two 13 bp inverted repeat sequences, flanking a central, 8 bp, directional core (Smith 2011). Artificially engineering these LoxP sequences into DNA regions flanking a target locus of interest ‘primes’ that site for recombination by Cre Recombinase (Kwan 2002).
The availability of the receptor cDNA ushered in a new era of molecular and structural investigation of AR action. The human receptor has up to 919 amino acids and a molecular weight of 110 kDa. The exact number of amino acids varies due to polymorphisms in two stretches of the amino acids glutamine (Q) and glycine (G) present in the N-terminal domain (NTD) (Fig. 2) (reviewed in McEwan 2004). AR gene/ mRNA Exon 1 Exon 2 TAU-1 Exon 3 Exon 4 Exon 5 Exon 6 Exon 7 Exon 8 TAU-5 LBD DBD AR Protein 1 Q G Transactivation (AF1) Protein-Protein Interactions 538 627 671 DNA NLS Binding 919 Steroid Binding Dimerisation Hsp90 binding Transactivation (AF2) Fig.