Steroid effects on neuronal activity: when is the genome involved?
For over four decades steroids have been regarded first as facilitators of enzymic reactions and subsequently as activators of genomic activity. The brain, long studied in terms of its bioelectric properties and anatomical connectivity, has now been recognized as a complex target tissue for genomic effects of steroid hormones, which bring about long-lasting alterations in brain structure and neurochemistry as well as changes in behaviour and neuroendocrine function. Studies of steroid effects on brain bioelectric activity have also shown rapid effects which are difficult to explain by a strictly genomic mechanism. One way to distinguish between genomic and non-genomic effects is by the time course, with extremely rapid effects being non-genomic and delayed effects being genomic. Effects with onset latencies of minutes to an hour may be due to either mechanism. Examples illustrating genomic actions include delayed effects of oestrogen which alter oxytocin and GABAA receptors and induce spines on dendrites and delayed glucocorticoid effects on neuronal survival. There are also examples of apparent genomic effects of oestradiol which interact with rapid and apparently non-genomic effects of progesterone: progesterone rapidly promotes spread of oestrogen-induced oxytocin receptors in ventromedial hypothalamus and rapidly modifies oestrogen-regulated GABAA receptor density in hypothalamus. The former effect is one produced by progesterone itself whereas the latter effect may be related to the ability of progesterone metabolites to interact with the chloride channel of the GABAA-benzodiazepine receptor complex.
McEwen
B S
BS
Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.
Coirini
H
H
Schumacher
M
M
D000818:Animals; D005260:Female; D015698:Genomic Library; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D051381:Rats; D013256:Steroids / Q000502:physiology*; D013963:Thyroid Hormones / Q000235:genetics
D018377:Neurotransmitter Agents; D013256:Steroids; D013963:Thyroid Hormones