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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.

	Abstract

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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.

	Introduction

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ANGIOTENSIN II (Ang II) may modulate directly or indirectly anterior pituitary hormone release. In the anterior pituitary, Ang II directly increases the release of ACTH and PRL (1). Indirect effects occur through the hypothalamus, where Ang II increases GnRH, CRF, and dopamine release, leading to an increase in LH and ACTH and a decrease in PRL release (1, 2, 3). Thus, brain and pituitary Ang II may regulate anterior pituitary hormone release by synergic or opposite effects.

The pituitary renin-angiotensin system has been recently reviewed by several researchers (4, 5). In the rat, pituitary Ang II is synthesized in gonadotropes, where it is stored and released together with LH. In this way, Ang II can stimulate the secretion of PRL and ACTH in a paracrine manner through interaction with specific angiotensin receptors (1). Two pharmacologically different Ang II receptor types, type 1 (AT₁) and type 2 (AT₂), have been identified using selective nonpeptidic and pseudopeptidic antagonists. The effects of Ang II on pituitary hormone release are mediated by AT₁ receptors (5).

The cloning of the AT₁ receptor complementary DNA (cDNA) revealed that it belongs to the seven-transmembrane domain, G protein-coupled receptor family and has led to the identification of two AT₁ receptor isoforms in rodents (6, 7), which have been designated AT_1A and AT_1B. In the rat, AT_1A and AT_1B cDNAs share 95% identity of the nucleotide sequence within their coding region, whereas the homology is reduced to 35% within the 5'- and 3'-untranslated regions (7). Stable expression of AT_1A and AT_1B in CHO cells shows comparable binding and coupling properties for both subtypes (8), preventing pharmacological differentiation. The intracellular signaling pathways of both receptors include coupling to a GTP-binding protein, activation of a phospholipase C resulting in inositol trisphosphate generation, mobilization of intracellular Ca²⁺ stores, and diacylglycerol formation leading to protein kinase C activation (6, 7). However, AT_1A and AT_1B messenger RNAs (mRNAs) are differentially expressed and regulated in various peripheral tissues (7, 9, 10, 11, 12), suggesting that the two receptor subtypes may mediate different biological actions of Ang II. In a previous study we have shown by in situ hybridization that AT_1A mRNA is predominantly expressed in the rat forebrain and that, in contrast, the AT_1B subtype dominates in the anterior pituitary (13). Thus, neuroendocrine effects of Ang II might occur not only at different levels but also through two different receptor subtypes. As gene expression of both receptor subtypes appears to be differentially regulated, the net effects of Ang II on pituitary hormone release may vary under different pathophysiological conditions.

However, the exact cellular localization of Ang II receptors in the intact pituitary is currently not known. Thus, the aim of the present study was to determine the phenotype of the endocrine cells expressing AT_1B receptor mRNA in the anterior pituitary of adult male Sprague-Dawley rats using in situ hybridization in combination with immunohistochemistry.

	Materials and Methods

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Synthesis of complementary RNA (cRNA) probes
The AT_1A antisense and sense and the AT_1B antisense cRNA probes were synthesized by in vitro transcription as previously described in detail (14). Briefly, two 2.2-kb cDNA fragments (clone pCa18b for AT_1A, a gift from Dr. K. Bernstein, and clone RAG6D4.60 for AT_1B, a gift from Dr. K. Sandberg) were subcloned into Bluescript KS plasmid (Stratagene, La Jolla, CA) and pCDNA II plasmid (Invitrogen, Oxon, UK), respectively. After linearization, in vitro transcription was performed using T3, T7, and SP6 RNA polymerases (Boehringer Mannheim, Mannheim, Germany) using [³⁵S]UTP (SA, 2000 Ci/mmol; Amersham, Les Ullis, France) and unlabeled ATP, GTP, and CTP (Boehringer Mannheim). The adequacy and the yield of the transcription were verified by agarose gel electrophoresis and scintillation count, as previously described (15). The specificity of the probes was previously demonstrated on CHO cells stably expressing either AT_1A or AT_1B receptors (13). Due to the construction of the gift AT_1B plasmid RAG6D4.60, only antisense, but no sense, AT_1B probes could be synthesized; thus, we used the AT_1A sense probe as the control probe for both the AT_1A antisense and the AT_1B antisense probes, as previously described (11, 13, 16).

Tissue preparation
All animal experiments were carried out in accordance with current institutional guidelines for the care and use of experimental animals. Adult (250–350 g) male Sprague-Dawley rats (n = 6) were kept on 12-h light, 12-h dark cycle with free access to food and water. Under pentobarbital anesthesia, rats were perfused transcardially after a brief saline rinse with 4% paraformaldehyde dissolved in PBS. Pituitaries were removed and postfixed overnight in the same fixative, then embedded in paraffin using standard procedures. Five-micron thick coronal sections were made and collected on 3-aminopropyltriethoxysilane (Sigma-Aldrich Co., L’Isle D’Abeau Chesnes, France) -coated slides.

In situ hybridization
After treatment with proteinase K, sections were hybridized with the AT_1B antisense and sense cRNA probes (see technical details in Ref. 17). For the detection of certain pituitary hormones, proteinase K treatment was omitted (see below). After washes at different temperatures and stringencies, including a ribonuclease treatment, the sections were processed for immunohistochemistry.

Antibodies
Antirat PRL, antirat LH, antirat LHß, antirat TSHß, antihuman ACTH, and antihuman FSHß antibodies were provided by the National Hormone and Pituitary Program, NIDDK. The specificities of these antisera were assessed by the NIDDK. The usable dilution was determined empirically for each antiserum (Table 1).

Immunohistochemistry after in situ hybridization
Immediately after in situ hybridization, the sections were rinsed twice in PBS and incubated in 20% normal goat serum for 20 min, then with different dilutions of primer antibodies (Table 1) for 90 min. After rinsing twice in PBS, sections were incubated in a 1:200 dilution of biotinylated antirabbit antibody (Vector, Compiegne, France) for 30 min, then rinsed again twice in PBS. Color reaction was developed with the Elite Vectastain Kit (Vector) using diaminobenzidine (DAB) as chromogene. The sections were washed in Tris-HCl buffer (50 mM; pH 7.6) overnight, dehydrated, dipped in Ilford K5 liquid emulsion, and exposed for 1 week.

Quantification of the double labeling
Quantification was carried out by two independent observers (Z.L. and A.M.N.), using a fluorescent microscope with a x40 objective coupled to a video image analysis system (NIH Image of Wayne Rasband) running on a Macintosh computer. AT_1B-expressing cells, labeled by the accumulation of silver grains over their cytoplasm (Fig. 1A), were visualized first using darkfield epifluorescence illumination (Fig. 1B), and their outlines were marked (Fig. 1C). Only cells containing more than 10 silver grains were considered positive. The marked outlines of the cells were maintained, and the illumination was changed to brightfield to visualize the immunohistochemical labeling (Fig. 1D). The presence of DAB-labeled cells was verified inside the marked outlines to count the single or double labeled cells. Secondly, the inverse process was performed as immunolabeled cells were outlined, and the illumination was changed to darkfield again to visualize the possible radioactive label of the immunolabeled cells. The total number of analyzed cells was at least 1000 for each hormone. Cells that were in the outer 200-µm zone of the anterior pituitary were considered cells of the peripheral zone.

View larger version (46K): [in this window] [in a new window]   Figure 1. Example of the quantification procedure of double labeling. Brightfield epifluorescence photomicrograph showing simultaneous detection of ACTH immunoreactivity, revealed by the dark DAB precipitate, and the expression of AT1B mRNA, revealed by bright silver grains (A). The same section with darkfield illumination is shown in B. The outlines of AT1B mRNA-expressing cells are marked in C. Brightfield visualization of the immunohistochemical labeling, with the cell outlines from C maintained, is shown in D. Some double labeled cells are marked with arrowheads, some AT1B-only cells are labeled with open arrows, and some AT1B negative, but immunopositive, cells are labeled with closed arrows. Scale bar = 50 µm.

Differences were considered significant at P < 0.05. Results are expressed as the mean ± SE.

	Results

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In situ hybridization
No cellular labeling was found with the AT_1A sense control probe (Fig. 2B). Hybridization signal with the AT_1A antisense probe was somewhat higher than that with the AT_1A sense probe, but the labeling was homogeneous and was not localized to individual cells (data not shown, published previously in Ref. 13). Hybridization with the AT_1B antisense probe resulted in well localized cellular labeling in 33.9 ± 1.0% of cells of the anterior pituitary lobe (Fig. 2A). The intermediate and posterior lobes showed no specific hybridization signal. AT_1B labeling appeared more prominent in the peripheral zone of the anterior pituitary than in the central zone of this organ (Fig. 2A), but the quantitative analysis did not yield a statistically significant difference (P > 0.05) in the percentage of labeled cells between the two zones.

View larger version (37K): [in this window] [in a new window]   Figure 2. Darkfield photomicrographs showing the labeling of the anterior pituitary obtained using the AT1B antisense (A) and the control (AT1A sense probe; B) on adjacent sections. A high expression of AT1B mRNA is detected in the anterior lobe (APit) in A. Note the complete lack of labeling in the posterior (PPit) and intermediate (IPit) lobes.

Expression of AT_1B receptor mRNA was detected only in PRL-immunoreactive (PRL-IR; Fig. 3A) and ACTH-IR cells (Fig. 3B). There was no detectable AT_1B mRNA expression in GH-IR (Fig. 3C), LH-IR (Fig. 3D), FSHß-IR (Fig. 3E), or TSHß-IR (Fig. 3F) cells.

View larger version (124K): [in this window] [in a new window]   Figure 3. Brightfield photomicrographs using epifluorescence illumination showing simultaneous detection of AT1B receptor mRNA and PRL (A), ACTH (B), GH (C), LH (D), FSHß (E), and TSH (F) in the anterior pituitary of the adult male rat. Some double labeled cells are marked with arrowheads, some AT1B-only cells are labeled with open arrows, and some AT1B negative, but immunopositive, cells are labeled with closed arrows. Note the important colocalization of the immunohistochemistry and in situ hybridization (bright dots) signals in lactotropes (A) and to a lesser degree in corticotropes (B) and the lack of expression of AT1B receptor mRNA in somatotropes (C), gonadotropes (D and E), and thyrotropes (F). Scale bars = 20 µm.

ACTH. For 1080 cells examined, 544 were labeled for AT_1B mRNA only, 407 were labeled for ACTH only, and 129 were labeled for both AT_1B mRNA and ACTH. After the construction and analysis of 14 datasets, 18.3 ± 2.1% of AT_1B receptor mRNA-expressing cells were immunoreactive for ACTH, and 21.5 ± 2.8% of all ACTH-IR cells were labeled for AT_1B mRNA.

	Discussion

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Our results show that in the adult male rat, an important fraction (about one third) of all anterior pituitary cells express AT_1B receptor mRNA. AT_1B receptor mRNA is expressed predominantly by PRL-IR and to a lesser extent by ACTH-IR cells, whereas no expression was found in GH-IR, LH-IR, TSHß-IR, or FSHß-IR cells. In contrast to that of AT_1B, AT_1A receptor mRNA expression could not be localized in individual cells. It is likely that the amount of AT_1A mRNA in the anterior pituitary is below the limit of detection in this experimental model.

A major part (78.2 ± 2.1%) of AT_1B-expressing anterior pituitary cells are immunoreactive for PRL, and another 18.2 ± 2.1% are immunoreactive for ACTH, accounting for 96.4% of all AT_1B mRNA-expressing cells. As the SD of both values is about 10%, it seems reasonable to conclude that detectable amounts of AT_1B mRNA are present only in these two types of anterior pituitary cells. As no expression of AT_1B mRNA was found in GH-IR cells, it is likely that mammosomatotroph cells, which are known to contain both PRL and GH (reviewed in Ref. 19) do not express a detectable amount of angiotensin receptor mRNA in the pituitary of adult male rats.

Our findings are in agreement with results of a recent study (20) in which we measured the amounts of AT_1A and AT_1B mRNA by quantitative RT-PCR in gradient-separated fractions of dispersed anterior pituitary cells. In this study, a relatively high density of angiotensin-binding sites and a high level of AT_1B mRNA were found in fractions containing lactotropes and corticotropes, but not in fractions containing mammosomatotropes, somatotropes, gonadotropes, or thyrotropes. In this report, 10–15% of all AT₁ receptor mRNA was of the AT_1A subtype and located in the same fractions as the AT_1B mRNA, a result that may be explained by the higher sensitivity of the RT-PCR technique compared with in situ hybridization. Interestingly, after the dispersed anterior pituitary cells had been kept 5 days in culture, the initial amount of total AT₁ receptor mRNA was decreased 5- to 7-fold, showing the importance of paracrine and growth factors in the maintenance of receptor expression by pituitary cells. To our knowledge, the present study is the first to investigate cellular localization of angiotensin receptors in intact pituitary. As in this organ, cell to cell interactions seem to play an important role in the phenotype of the hormone-producing cells (21), it is important to study the expression of receptors in intact tissue.

The presence of angiotensin receptors on anterior pituitary cells was also investigated by Paglin et al. (22) by morphological analysis of dispersed pituitary cells binding Ang II. According to morphological criteria at the light and electron microscopic levels, the angiotensin-binding cells were identified as mammotropes, corticotropes, and presumptive thyrotropes; the latter cell type was not clearly distinguishable from mammotropes with their experimental method. In accordance with these results, our study shows that the AT_1B receptor mRNA is expressed in mammotropes and corticotropes, but is absent in other hormone-producing cells, including thyrotropes. Thus, considering our current findings, it is likely that the "presumptive thyrotropes" of their study were instead PRL-synthesizing cells.

As only about half of all PRL-IR cells and about a quarter of all ACTH-IR cells expressed AT_1B mRNA, our results suggest a heterogeneity in the sensitivity to Ang II of these cell populations. Indeed, in PRL cells, the existence of both morphological and functional heterogeneities is known (23, 24). Subpopulations of PRL cells were found to exhibit differences in resting and induced PRL secretion, passive membrane properties, Ca²⁺ currents, and responses to stimuli such as Ang II, TSH, or dopamine (25, 26, 27). This heterogeneity is probably a means of optimizing the secretory response to the complex regulatory influences on the pituitary.

The in vivo stimulation of PRL release by peripherally injected Ang II increases with age, and first responses were observed at 20 days of age in both sexes in rats (28). However, physiological doses of Ang II (0.01–10 nM) can stimulate PRL release only from cells collected from mature female rats (29). Several physiological stimuli were found to influence the Ang II-mediated PRL release. Suckling induces a proportional shift between different subpopulations of PRL cells toward those cells most responsive to stimulatory secretagogues (such as Ang II and TRH) and away from those most susceptible to inhibition by dopamine (30). Estradiol has a direct inhibitory action on the expression of pituitary AII receptors, but this is not accompanied by a decrease in AII-stimulated PRL secretion (20, 31). Therefore, physiological studies suggest that the proportion of PRL-IR cells expressing AT_1B receptors may vary in different pathophysiological conditions.

Our results suggest that Ang II exerts its direct stimulatory effect on ACTH release in anterior pituitary cells via AT_1B receptors synthesized in corticotropes. The fact that only a subpopulation of corticotropes contains AT_1B receptor mRNA is not surprising, as corticotropes are also heterogeneous in size, shape, storage patterns, and secretory responses (reviewed in Ref. 32). Several factors, such as cold, novel environment, ion channel blockers, corticosterone, and secretagogues such as CRH or epidermal growth factor, modulate the percentage of ACTH-IR or POMC mRNA-expressing cells as well as the percentage of cells that bind CRH and store ACTH (32). Ang II also increases the percentage of cells that bind CRH and store ACTH (32). The rapid changes in cell percentages with the different treatments suggest the existence of reserve cells that may be sensitive to certain levels of different types of stimuli. Identification of the functional role of the corticotroph subpopulation that contains AT_1B mRNA, identified in the present study, needs further investigations.

In conclusion, the present study establishes for the first time that about one third of the cells in the intact anterior pituitary of male rats may be directly regulated by Ang II through their expression of AT_1B receptor mRNA. These cells correspond in a major part to a subpopulation of mammotroph cells and to a lesser part to a subpopulation of corticotroph cells. Thus, this work provides a morphological base for further studies exploring the physiological role of Ang II in the regulation of anterior pituitary functions.

	Acknowledgments

 
The authors thank the National Hormone and Pituitary Program, the NIDDK, the NICHHD, and the USDA for the kind gift of antibodies.

	Footnotes

 
¹ Supported by a fellowship from the Medical Research Council of Canada.

Received March 30, 1998.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Ganong WF 1989 Angiotensin II in the brain and pituitary: contrasting roles in the regulation of adenohypophyseal secretion. Horm Res 31:24–31[CrossRef][Medline]
2. Phillips MI 1987 Functions of angiotensin in the central nervous system. Annu Rev Physiol 49:413–435[CrossRef][Medline]
3. Kordon C, Drouva SV, Martinez de la Escalera G, Weiner RI 1994 Role of classic and peptide neuromediators in the neuroendocrine regulation of luteinizing hormone and PRL. In: Knobil E, Neill J (eds) The Physiology of Reproduction. Raven Press, New York, pp 1621–1681
4. Saavedra JM 1992 Brain and pituitary angiotensin. Endocr Rev 13:329–380[CrossRef][Medline]
5. Ganong WF 1993 Blood, pituitary, and brain renin-angiotensin systems and regulation of secretion of anterior pituitary gland. Front Neuroendocrinol 14:233–249[CrossRef][Medline]
6. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE 1991 Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 351:233–236[CrossRef][Medline]
7. Sandberg K 1994 Structural analysis and regulation of angiotensin II receptors. Trends Endocrinol Metab 5:28–35
8. Clauser E, Curnow KM, Conchon S, Davies E, Teutsch B, Vianello B, Monnot C, Corvol P 1995 Molecular structure and mechanisms of action of mammalian angiotensin receptors. Curr Opin Endocrinol Diabetes 2:404–411
9. Iwai N, Inagami T, Ohmichi N, Nakamura Y, Saeki Y, Kinoshita M 1992 Differential regulation of rat AT1a and AT1b receptor mRNA. Biochem Biophys Res Commun 188:298–303[CrossRef][Medline]
10. Burson JM, Aguilera G, Gross KW, Sigmund CD 1994 Differential expression of angiotensin receptor 1A and 1B in mouse. Am J Physiol 267:E260–E267
11. Gasc JM, Shanmugam S, Sibony M, Corvol P 1994 Tissue-specific expression of type 1 angiotensin II receptor subtypes. An in situ hybridization study. Hypertension 24:531–537[Abstract/Free Full Text]
12. Llorens-Cortes C, Greenberg B, Huang H, Corvol P 1994 Tissular expression and regulation of type 1 angiotensin II receptor subtypes by quantitative reverse transcriptase-PCR analysis. Hypertension 24:538–548[Abstract/Free Full Text]
13. Lenkei Z, Corvol P, Llorens-Cortes C 1995 The angiotensin receptor subtype AT1A predominates in rat forebrain areas involved in blood pressure, body fluid homeostasis and neuroendocrine control. Mol Brain Res 30:53–60[Medline]
14. Shanmugam S, Monnot C, Corvol P, Gasc J-M 1994 Distribution of type 1 angiotensin II receptor subtype messenger RNAs in the rat fetus. Hypertension 23:137–141[Abstract/Free Full Text]
15. Gasc JM, Monnot C, Clauser E, Corvol P 1993 Co-expression of type 1 angiotensin II receptor (AT1R) and renin mRNAs in juxtaglomerular cells of the rat kidney. Endocrinology 132:2723–2725[Abstract]
16. Shanmugam S, Corvol P, Gasc JM 1994 Ontogeny of the two angiotensin II type 1 receptor subtypes in rats. Am J Physiol 267:E828–E836
17. Sibony M, Commo F, Callard P, Gasc JM 1995 Enhancement of mRNA in situ hybridization signal by microwave heating. Lab Invest 73:586–591[Medline]
18. Duhau L, Grassi J, Grouselle D, Enjalbert A, Grognet JM 1991 An enzyme immunoassay for rat PRL: application to the determination of plasma levels. J Immunoassay 12:233–250[Medline]
19. Frawley LS, Boockfor FR 1991 Mammosomatotropes: presence and functions in normal and neoplastic pituitary tissue. Endocr Rev 12:337–355[Medline]
20. Moreau C, Rasolojanahary R, Zamora AJ, Enjalbert A, Kordon C, Llorens-Cortes C 1997 Expression of angiotensin II receptor subtypes AT(1A) and AT(1B) in enriched fractions of dispersed rat pituitary cells. Neuroendocrinology 66:416–425[Medline]
21. Vankelecom H, Denef C 1997 Paracrine communication in the anterior pituitary as studied in reaggregate cell cultures. Microsc Res Technol 39:150–156[CrossRef][Medline]
22. Paglin S, Stukenbrok H, Jamieson JD 1984 Interaction of angiotensin II with dispersed cells from the anterior pituitary of the male rat. Endocrinology 114:2284–2292[Abstract]
23. Tougard C, Tixier-Vidal A 1988 Lactotropes and gonadotropes. In: Knobil E, Neill J (eds) The Physiology of Reproduction. Raven Press, New York, pp 1305–1333
24. Vila-Porcile E, Barret A 1996 Structural and functional differences between PRL cells from the inner and outer zones of the male rat anterior pituitary. Cell Tissue Res 284:247–259[CrossRef][Medline]
25. Winiger BP, Wuarin F, Zahnd GR, Wollheim CB, Schlegel W 1987 Single cell monitoring of cytosolic calcium reveals subtypes of rat lactotrophs with distinct responses to dopamine and thyrotropin-releasing hormone. Endocrinology 121:2222–2228[Abstract]
26. Lledo PM, Guerineau N, Mollard P, Vincent JD, Israel JM 1991 Physiological characterization of two functional states in subpopulations of PRL cells from lactating rats. J Physiol (Lond) 437:477–494[Abstract/Free Full Text]
27. De Paul A, Pons P, Aoki A, Torres A 1997 Different behavior of lactotroph cell subpopulations in response to angiotensin II and thyrotrophin-releasing hormone. Cell Mol Neurobiol 17:245–258[CrossRef][Medline]
28. Diaz-Torga GS, Becu-Villalobos D, Libertun C 1994 Ontogeny of angiotensin-II-induced PRL release in vivo and in vitro in female and male rats. Neuroendocrinology 59:57–62[Medline]
29. Janik JM, Robinson EO, Shen J, Callahan P 1997 Effects of age and gender on the AII-induced stimulation of PRL release and inositol phosphate accumulation in rat anterior pituitary cells in vitro. Mech Ageing Dev 95:113–130[CrossRef][Medline]
30. Nagy GM, Frawley LS 1990 Suckling increases the proportions of mammotropes responsive to various PRL-releasing stimuli. Endocrinology 127:2079–2084[Abstract]
31. Platia MP, Catt KJ, Aguilera G 1986 Effects of 17 beta-estradiol on angiotensin II receptors and PRL release in cultured pituitary cells. Endocrinology 119:2768–2772[Abstract]
32. Childs GV 1992 Structure-function correlates in the corticotropes of the anterior pituitary. Front Neuroendocrinol 13:271–317[Medline]

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