Effects of LHRH and ANG II on prolactin stimulation are mediated by hypophysial AT1 receptor subtype.
We have used the nonpeptide angiotensin II (ANG II) receptor antagonists losartan (receptor subtype AT1) and PD-123319 (AT2) to determine the participation of ANG II receptor subtypes in luteinizing hormone-releasing hormone (LHRH)-induced prolactin release in a perifusion study using intact pituitaries in vitro. LHRH (1.85 x 10(-7) M) released prolactin consistently, whereas losartan (10(-5) M) abolished prolactin response without modifying basal prolactin or luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release. PD-123319 (10(-5) M) had no effect on basal or LHRH-induced prolactin, LH, or FSH release. We also determined that the effect of ANG II on prolactin release was mediated by the same receptor subtype. In adenohypophysial cells dispersed in vitro ANG II (10(-8) M) released prolactin. Losartan (10(-7) and 10(-6) M), but not PD-123319, inhibited this effect. We conclude that in intact hypophyses of 15-day-old female rats the effect of LHRH on prolactin release is readily demonstrated. LHRH-induced prolactin release appears to be mediated by ANG II acting in a paracrine manner on AT1 receptors located on lactotrophs.
Becú-Villalobos
D
D
Laboratorio de Neuroendocrinología, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina.
Lacau-Mengido
I M
IM
Thyssen
S M
SM
Díaz-Torga
G S
GS
Libertun
C
C
D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D010477:Perfusion / Q000379:methods; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D007987:Gonadotropin-Releasing Hormone; D011388:Prolactin; D019808:Losartan