Effects of Angiotensin II and Atrial Natriuretic Peptide on LH Release are Exerted in the Preoptic Area: Possible Involvement of Gamma-Aminobutyric Acid (GABA)

Summary

The preoptic/anterior hypothalamic area (PO/AH) contains the majority of LHRH neurons of which the function is regulated by a variety of neuro-transmitters and peptides. In this area, numerous estrogen-receptive neurons utilize gammaaminobutyric acid (GABA) as neurotransmitter and these neurons communicate directly with LHRH neurons. Angiotensin II (AII) and atrial natriuretic peptide (ANP) are known to be involved in the regulation of LH secretion. The site of action of these peptides and the mechanisms by which they influence LHRH neurons, are largely unknown. Therefore the effects of intrapreoptic application of All and ANP on serum LH levels of ovariectomized (ovx) and of ovx estrogen-primed rats were investigated. The peptides were applied into the PO/AH by means of push-pull cannula and in the effluent fractions GABA was measured.

In the ovx estrogen-primed rat, prominent LH and prolactin surges were observed. At the time of increased LH levels preoptic GABA release was significantly reduced.

At this time application of AII or ANP into the PO/AH was without effect on either LH or prolactin levels in the serum or on preoptic GABA release rates. In ovx, not steroid-primed rats intrapreoptic All application suppressed serum LH levels significantly and this treatment had a slight stimulatory effect on preoptic GABA release rates. This effect of AII could be antagonized by prior preoptic treatment with saralasin, a specific All receptor blocking peptide. Preoptic treatment with ANP resulted in a slight increase in serum LH levels which was accompanied by a slight, but significant reduction of preoptic GABA release rates.

It is concluded that neither AII nor ANP are significantly involved in the regulation of the estrogen-induced LH and prolactin surges whereas in ovx rats AII has a strong inhibitory action on the function of LHRH neurons.

This latter effect is at least in part mediated by GABAergic neurons. The effect of AII appears to be mediated by specific receptors as saralasin completely prevented the AII-mediated inhibition of LH secretion. ANP had a slight inhibitory effect on preoptic GABA release rates, thereby it stimulated LHRH release as demonstrated by increased serum LH levels.

Key words

Angiotensin II - ANP - preoptic area - LH release - GABA