title: Stimulation of prolactin secretion from rat pituitary by luteinizing hormone-releasing hormone: evidence against mediation by angiotensin II acting through a (Sar1-Ala8)-angiotensin II-sensitive receptor.
abstract: In aggregate cell cultures of 15- to 20-day-old rat pituitary maintained in serum-free medium, luteinizing hormone-releasing hormone (LHRH) (10 nM) stimulated prolactin (PRL) release, confirming our previous results and those of others with serum-supplemented medium. Since angiotensin II (AII) stimulates PRL release and a renin-angiotensin system is expressed in gonadotrophs, LHRH stimulation of PRL release might be mediated by AII. To evaluate this hypothesis, the influence of (Sar1,Ala8)AII and (Sar1,Ile8)AII two peptide AII receptor antagonists, of DUP753, a nonpeptide and stable AII receptor antagonist, of a converting enzyme inhibitor, and of angiotensinogen on LHRH-induced PRL release was tested in various in vitro conditions of 15- to 20-day-old female rat pituitary. In aggregates maintained in serum-free medium with or without dexamethasone (DEX) and triiodothyronine (T3), or maintained in serum-supplemented medium, the effect of LHRH on PRL release was not affected by (Sar1Ala8)AII (0.1 microM), (Sar1,Ile8)AII (10 microM) or DUP753 (10 microM). Only a high dose (10 microM) of (Sar1,Ala8)AII attenuated the LHRH-induced PRL release. The latter attenuation was seen only with aggregates cultured in the DEX/T3 medium and not with aggregates cultured in the presence of serum. A dose of 1 or 10 nM (Sar1,Ala8)AII also failed to block the effect of LHRH used at 1 nM. In contrast, (Sar1,Ala8)AII dose dependently as well as DUP753 (10 microM) abolished the AII-induced PRL release. (Sar1,Ala8)AII also failed to affect the LHRH-induced PRL release in pituitary cell aggregates from 6-week-old male rats. However, in aggregates from both immature and 6-week-old rats, (Sar1,Ala8)AII provoked a small and statistically significant attenuation of the LHRH-induced PRL release when a 100 nM dose of LHRH was used. In freshly isolated hemipituitaries from 5-day-old rats, (Sar1,Ala8)AII (1 or 10 microM) did not affect the LHRH- (10 nM) induced PRL release. In single cells obtained by redispersion of aggregates and mounted in a Biogel P2 column, LHRH still stimulated PRL release. Again this effect could not be blocked by DUP753. Treatment of aggregate cell cultures with the angiotensin-converting enzyme inhibitor captopril or with angiotensinogen did not alter the LHRH-induced PRL release. It is concluded that AII is not the paracrine factor mediating the effect of LHRH at low nanomolar doses on PRL release, at least not through the classical AII receptor. The involvement of AII acting on a non-(Sar1,Ala8)AII-sensitive receptor cannot be excluded and warrants further investigation.
authors.affiliation: Laboratory of Cell Pharmacology, University of Leuven, School of Medicine, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Robberecht
authors.forename: M
authors.initials: M
authors.lastname: Andries
authors.forename: C
authors.initials: C
authors.lastname: Denef
mesh_terms: D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology*; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000808:Angiotensinogen; D000804:Angiotensin II; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D002216:Captopril; D012504:Saralasin; D019808:Losartan