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Identification of Endocrine Cell Populations Expressing the AT_1B Subtype of Angiotensin II Receptors in the Anterior Pituitary

INSERM U-36, Chaire de Médecine Expérimentale, Collège de France (Z.L., A.M.N., P.C., C.L.-C.), 75005 Paris; and INSERM U-159, Institut Paul Broca (D.G.), 75014 Paris, France

Address all correspondence and requests for reprints to: Dr. C. Llorens Cortes, INSERM U-36, Chaire de Médecine Expérimentale, Collège de France, 3 rue d’Ulm, 75005 Paris, France.

Angiotensin II (Ang II) participates in the regulation of anterior pituitary hormone secretion by acting either directly on the anterior pituitary or indirectly on the hypothalamus. When applied directly on pituitary cells, Ang II increases both ACTH and PRL secretion and has also been reported to affect GH secretion. Three distinct subtypes of Ang II receptors (AT_1A, AT_1B, and AT₂) have been identified; they are unequally distributed and differently regulated in various tissues. We have previously demonstrated that only AT_1A receptors are present in the hypothalamus while anterior pituitary cells express predominantly the AT_1B subtype. Using in situ hybridization in combination with immunohistochemistry, the aim of the present study was to identify the phenotype of the endocrine cell expressing AT_1B receptor messenger RNA (mRNA) in the anterior pituitary of adult male Sprague-Dawley rats. Expression of AT_1B receptor mRNA was present in 33.9 ± 1.0% of anterior pituitary cells. AT_1B mRNA is predominantly expressed by lactotropes (78.2 ± 2.1% of AT_1B mRNA-expressing cells) and to a lower degree by corticotropes (18.3 ± 2.1%) and is not detectable in somatotropes, mammosomatotropes, gonadotropes, or thyrotropes. These results indicate that in adult male rats, Ang II, which has been shown to be synthesized in gonadotropes, can directly stimulate PRL and ACTH release from lactotropes and corticotropes through activation of AT_1B receptors. As only 53.8 ± 2.7% of lactotropes and 23.6 ± 2.8% of corticotropes expressed AT_1B mRNA, our findings suggest a functional heterogeneity of both cell types regarding their sensitivity to Ang II.

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