Steroid control of central neuronal interactions and function.
Steroids have potent actions on the brain which can be categorized as; (i) fast (approximately ms-s), (ii) intermediate (h-days), (iii) long-term reversible (days-weeks) and (iv) long-term irreversible. Here attention is focussed on the intermediate and long-term reversible effects of steroids with emphasis on glucocorticoids and oestrogen. Glucocorticoid negative feedback is generally classified as fast, delayed and long-term. Fast negative feedback would appear to depend mainly on a reduction in pituitary responsiveness to corticotrophin releasing factor-41 (CRF-41) and possibly arginine vasopressin (AVP). Delayed feedback is mediated by reduced AVP release into hypophysial portal blood and blockade of the ACTH response to CRF-41. Long-term negative feedback is a consequence of reduced CRF-41 and AVP release into portal blood. Lesion and electrical stimulation studies pinpoint the paraventricular nuclei as the main site at which glucocorticoids act to control ACTH release. Oestrogen at physiologically low plasma concentrations inhibits gonadotrophin secretion. At physiologically high plasma concentrations, such as those that occur during the preovulatory surge, oestradiol-17 beta stimulates the biosynthesis of LHRH mRNA and LHRH and the release of LHRH into hypophysial portal blood. Oestradiol also increases pituitary responsiveness to LHRH. The action of oestrogen on LHRH neurons is probably mediated by interneurons and may involve disinhibition; this view is supported by our in situ hybridization studies which show that oestrogen, in its positive feedback mode, significantly reduces the synthesis of proopiomelanocortin mRNA in arcuate neurons which when active are likely to inhibit LHRH neurons. The mechanism of action of oestrogen on the pituitary gland is not yet established, but clues from the action of the priming effect of LHRH suggests that oestrogen may potentiate phosphoinositide second messenger cascades. LHRH priming involves the synthesis of a 70 kDa protein the N-terminus of which is identical to an oestrogen-induced protein in the ventromedial hypothalamic nucleus involved in lordosis, and to that of phospholipase C alpha. Attention is drawn to the remarkable economy of the system by which a single steroid, oestrogen, has effects on the brain and pituitary gland which result in a co-ordinated sequence of amplifier cascades which lead first to the ovulatory surge of luteinizing hormone and then to mating behaviour, both of which are obviously essential for continuation of the species.(ABSTRACT TRUNCATED AT 400 WORDS)
Fink
G
G
MRC Brain Metabolism Unit, University Department of Pharmacology, Edinburgh, Scotland.
Rosie
R
R
Sheward
W J
WJ
Thomson
E
E
Wilson
H
H
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D004967:Estrogens / Q000502:physiology; D005260:Female; D006062:Gonadotropins / Q000502:physiology; D007031:Hypothalamus / Q000502:physiology; D011388:Prolactin / Q000502:physiology; D051381:Rats; D013256:Steroids / Q000502:physiology*
D004967:Estrogens; D006062:Gonadotropins; D013256:Steroids; D000324:Adrenocorticotropic Hormone; D011388:Prolactin