Hormone replacement therapy
Hormone replacement therapy (HRT), is a form of hormone treatment used to treat gender dysphoria, menopause symptoms or hypogonadism.
HRT makes the patient's body behave in a way typical of the opposite genetic sex in a very precise way. This occurs due to the nature of genetics and hormone signaling as is explained below. That is the reason why, for example, a person with complete androgen insensitivity syndrome has a 46,XY karyotype and yet is indistinguishable from a normal woman without a pelvic exam.
A gene is a segment of DNA which encodes a protein. They can be thought as a recipe of how to produce the protein. And since proteins are responsible for the overwhelming majority of the structure of living beings, the set of an organism's genes, its genome, is often said to be its blueprint. However many factors affect how genes are expressed, that is when and how often they actually encode protein, so genes do not alone determine an organism's phenotype. These factors include DNA methylation, non-coding DNA, other genes and the effects of nuclear receptors. In fact, nearly all traits people care about are encoded not by a single gene, but by a large collection of genes, known as a polygene.
In the 1990s, a major international project was undertaken to sequence the genome of a human being, the Human Genome Project. It was a massive project, costing 3 billion dollars, involving universities around the world and many of the world's most famous biologists over 15 years. And while it improved mankind's understanding of evolution and human physiology, the improvement of medicine as a result was disappointing. Rood and Rowen say:
We predict that individual genome sequences will soon play a larger role in medical practice. In the ideal scenario, patients or consumers will use the information to improve their own healthcare by taking advantage of prevention or therapeutic strategies that are known to be appropriate for real or potential medical conditions suggested by their individual genome sequence. Physicians will need to educate themselves on how best to advise patients who bring consumer genetic data to their appointments, which may well be a common occurrence in a few years.
They were correct that now it is cheap and easy to get your whole genome sequenced, but they were wrong that sequencing your genome provides a significant improvement in care for most patients. Unless you have something seriously wrong, the most you'll learn from having your genome sequenced is that you have slightly increased or decreased risks of many types of ailments. Another shocking finding is that 98% of the human genome is non-coding DNA. Therefore, in the words of Moraes and Góes:
The HGP and ENCODE projects contributed to the mapping of human genome and in the evolution of the central dogma of molecular biology. These studies revealed that the complexity of our genome does not rely in protein‐coding genes quantity but in a great network of transcripts that allows the interactions for genome regulation. The concept of the central molecular biology dogma was reformulated. There is no unidirectional flow of information from one class of molecule to another. All the process is feedback interconnected. We deviated from a strict genetic determinism. A gene‐centric conception of the organism has to be reviewed.[...] The key for understanding the “secret of life” has not been revealed.
In other words, genome is not destiny. Thus the groundwork for explaining the effects of HRT is laid, and the details are below.
Hormone receptors are a kind of nuclear receptor, specifically those used by an organism to signal certain things. They act by modulating gene expression, that is, by increasing or decreasing the production of certain proteins in certain circumstances. Thus the concentration of hormones in blood, and therefore in cells, alters what was laid by its genome to produce wildly varying outcomes. And since we called the genome a living being's blueprint, we may call this an alteration in the interpretation of the blueprint. These changes can be quite significant, for example congenital hypothyroidism (a deficiency of thyroid hormone in newborns) causes mental retardation when untreated.
The evolutionary purpose of hormones is to allow for the flexibility that having a central control on the gene expression of cells in the entire body enables. For example, the pancreas controls production of insulin, which in turn controls whether sugar in blood is converted into fat stores or the other way around. This means that the body can convert a large meal into fat one day and convert the stored fat back into a readily usable form the next day when it's needed for exercise. The pancreas has a more complex system for inquiring what the general metabolic state of the body is than any single cell could ever hope to have, so it's far more accurate.
We, armed with chemistry knowledge, can mess with these systems to our advantage. In the case of type 1 diabetes this means injecting insulin. This turns what was previously a death sentence into a prognosis of a largely normal life. We can also, of course, choose whether a person will develop a male or female phenotype.
The X and Y chromosomes
The X chromosome is very similar to the other 44 chromosomes, however the Y chromosome is significantly different. It encodes only 71 genes in comparison to an average of 443. Of those genes, one is the SRY gene, which causes the differentiation of gonads into testicles, the other seventy are related to sperm production and not much else. That is the reason why human beings can exist without a Y chromosome. For example Turner syndrome is most often a 45,X karyotype, that is, a normal male 46,XY karyotype subtracted of its Y chromosome. Its average diagnosis age is 15, often as amenorrhea starts to be concerning. That is, the non-reproductive effects of the absence of a Y chromosome are so subtle that often no diagnosis can be reached. Another example is mosaic loss of the Y chromosome, which happens in 15% of men over the age of 70. Again it is often not diagnosed.
The x chromosome on the other hand encodes many important proteins, for example dystrophin. That is the reason why Duchenne Muscular Dystrophy, a genetic diseas caused by a defect in the dystrophin gene, is x-linked. Other x-linked disorders include hemophilia and some types of color blindness, all of which are more common in men. However, in people with no x-linked disorders, the expression of genes present in the X chromosome is the same regardless of karyotype because of X chromosome inactivation. Inactivation happens in women when the second X chromosome, which is chosen at random, becomes a Barr body. Therefore, any human cell has exactly one active X chromosome producing protein.
- The Human Genome Project: big science transforms biology and medicine, Leroy Hood, Lee Rowen. pubmed sci-hub Genome Medicine, 2013.
- A decade of human genome project conclusion: Scientific diffusion about our genome knowledge, Fernanda Moraes, Andréa Góes. pubmed sci-hub Biochemistry and Molecular Biology, March 7th 2016.
- Hormone evolution: The key to signalling, Kushiro, T., Nambara, E. & McCourt, P. pubmed sci-hub , .
- Turner syndrome: mechanisms and management, Claus H Gravholt, Mette H Viuff, Sara Brun, Kirstine Stochholm , Niels H Andersen. pubmed sci-hub , .
- Mosaic loss of human Y chromosome: what, how and why, Xihan Guo, Xueqin Dai, Tao Zhou, Han Wang, Juan Ni, Jinglun Xue & Xu Wang. pubmed sci-hub , .