Question: Which hormones have the greatest epigenetic effect?

Elaine Marshall answered on 17 Jun 2013:

This is a really good question and one which there is much debate about just now. To answer which hormones have the greatest epigenetic effect would require in depth quantification of all the genes expressed in a cell when it is exposed to a hormone and compare this to all the genes expressed (transcribed) in the cell when it doesn’t see the hormone. This measurement could expect to vary between cells in the same organism as the same hormone may have different effect on different cells. Also the level of transcription may even change in the same cell types found in different organisms! As to which hormones have the greatest effect I am not sure but I believe the steroid hormones may be a potential leader….

I can only answer this question in any detail from the perspective of what happens in mammals. However it is important to recognise some of the most amazing developmental changes in nature occur in invertebrates and lower order vertebrates where hormones, such as thyroxine, leptin, androgens and ecdysteroids, are known to regulate metamorphosis.

Studies have shown the environmental factors a cell is exposed to during critical periods of early development (foetal development, puberty etc) can alter the behaviour/ appearance (phenotype) of the cell. This change in phenotype is brought about not by altering the cells inherited DNA sequence, but by a set of chemical reactions that alter how the cell’s DNA is read and ultimately result in determining which genes are switched on or off. Epigenetics is the study of these reactions and the factors that influence them. Several groups of enzymes are known to be key epigenetic modifiers of a cell’s DNA: these enzymes are involved in processes such as DNA methylation (adding methyl groups to specific sites along the DNA seq to silence gene expression) and histone modification (altering structure/accessibility of the protein scaffolding that the helix is wrapped around to form chromatin). Collectively these enzymes allow for packaging of genes into active or inactive areas of chromatin and can determine whether they accessible for the transcription machinery or not.

In mammals, the steroid hormones have been shown to exert epigenetic regulation of these enzymes in cells grown in culture (in vitro) and can therefore alter how a cell responses to its environment. For example it is known that in vitro the steroid hormones oestrogen, progesterone and androgen directly regulate the epigenetic modifying enzymes and directly alter gene expression. In one study in particular it was presented that these enzymes were involved in differentiation of the womb lining (endometrium). Recent studies have also shown that exposure to glucocorticoids (another member of the steroid family) during intrauterine development alters the methylation pattern in the developing offspring and affects adult phenotype and leads to abnormalities in a wide range of physiological systems much later in life. Finally there is evidence that steroids impact epigenetics from observations that exposure to chemicals resembling steroids (eg BPA, cadmium, etc) which mimic or disrupt an organisms normal endocrine response (mainly oestrogen and androgen) can alter normal development or influence gene expression.