Biol Reprod Email Content Delivery
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Coulter, C. L.
Right arrow Articles by Bird, I. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coulter, C. L.
Right arrow Articles by Bird, I. M.
Agricola
Right arrow Articles by Coulter, C. L.
Right arrow Articles by Bird, I. M.
Biology of Reproduction 62, 714-719 (2000)
© 2000 Society for the Study of Reproduction, Inc.

Articles

Ontogeny of Angiotensin II Type 1 Receptor and Cytochrome P450c11 in the Sheep Adrenal Gland1

Catherine L. Coulter2,a, Dean A. Myersb, Peter W. Nathanielszc, and Ian M. Birdd

a Department of Physiology, University of Adelaide, Adelaide, South Australia, Australia 5005 b Department of Physiology, College of Medicine, University of Oklahoma, Health Sciences Center, Oklahoma City, Oklahoma 73190 c Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401 d Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, Wisconsin 53715


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
In the present study we investigated the ontogeny of the expression of the type 1 angiotensin receptor (AT1R mRNA) and the zonal localization of AT1R immunoreactivity (AT1R-ir) and cytochrome P450c11 (CYP11B-ir) in the sheep adrenal gland. In the adult sheep and in the fetus from as early as 90 days gestation, intense AT1R-ir was observed predominantly in the zona glomerulosa and to a lesser extent in the zona fasciculata, and it was not detectable in the adrenal medulla. AT1R mRNA decreased 4-fold between 105 days and 120 days, whereas AT1R mRNA levels remained relatively constant between 120 days and the newborn period. In contrast, both in the adult sheep and in the fetal sheep from as early as 90 days gestation, intense CYP11B-ir was consistently detected throughout the adrenal cortex and in steroidogenic cells that surround the central adrenal vein. In conclusion, we speculate that the presence of AT1R in the zona fasciculata, and the higher levels of expression of AT1R at around 100 days gestation, may suggest that suppression of CYP17 is mediated via AT1R at this time. The abundant expression of AT1R-ir and CYP11B-ir in the zona glomerulosa of the fetal sheep adrenal gland would also suggest that lack of angiotensin II stimulation of aldosterone secretion is not due to an absence of AT1R or CYP11B in the zona glomerulosa.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The fetal adrenal gland synthesizes and secretes steroid hormones that regulate intrauterine homeostasis, the maturation of fetal organ systems necessary for extrauterine life, and, in species such as the sheep, the initiation of parturition [1]. After birth, the major role of the adrenal cortex is to provide glucocorticoids (cortisol) for the maintenance of metabolic homeostasis and response to stress, as well as mineralocorticoids (aldosterone) for maintenance of fluid and electrolyte balance, and regulation of blood pressure [1]. Therefore development of the fetal adrenal cortex preterm is critical for fetal maturation and postnatal survival.

In the fetal sheep, cytochrome P450 17 hydroxylase (CYP17) has been shown to be the pivotal enzyme in the regulation of the synthesis and secretion of cortisol from the fetal adrenal gland [2]. During development there is a period of steroidogenic quiescence (90–130 days gestation) when CYP17 enzyme expression is suppressed and the fetal sheep adrenal is also unresponsive to adrenocorticotropin (ACTH) stimulation [3]. In fetal sheep adrenal cells in vitro, administration of angiotensin II (AII) inhibits ACTH-induced expression of CYP17 and suppresses cortisol secretion [4]. These data suggest that AII may play an important role in the regulation of cortisol synthesis during fetal life.

In the adult adrenal, the synthesis and secretion of aldosterone are regulated through a specific receptor for AII, the type 1 angiotensin receptor (AT1R). In the fetal sheep adrenal, levels of aldosterone synthesis and secretion are very low until the final part of gestation [5]. In contrast to the adult, in the sheep fetus in utero, aldosterone concentrations do not rise in response to surgical stress, furosemide, AII, or ACTH [3, 6, 7]. These data suggest that AT1R may not be present or active in zona glomerulosa in the fetal adrenal gland.

In the sheep, one CYP11B gene has been isolated, and in vitro expression studies have shown that the product of this ovine CYP11B gene can catalyze the final steps in glucocorticoid synthesis, i.e., 11ß-hydroxylation for cortisol synthesis as well as 11ß-hydroxylation, 18-hydroxylation, and 18-oxidation necessary for aldosterone synthesis [8]. In the fetal sheep adrenal gland, previous studies have demonstrated the expression of CYP11B protein and mRNA using Western and Northern blot analyses, respectively [9, 10]. However, the ontogeny of the specific zonal localization of CYP11B in the fetal sheep adrenal gland remains to be determined. In this study, we have determined the ontogenetic expression of AT1R mRNA and the pattern of localization of AT1R immunoreactivity (AT1R-ir) and cytochrome P450c11 (CYP11B-ir) in the sheep adrenal gland in order to investigate their roles in regulating cortisol and aldosterone synthesis in utero.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Tissue Collection

In this study, all ewes were killed by an overdose of sodium pentobarbitone, administered intravenously. The fetuses were delivered by hysterotomy for collection of fetal adrenal tissue. Adrenal glands were collected from sheep fetuses at 105 days (n = 4), 120–129 days (n = 4), 136 days (n = 3), and at birth (n = 3; vaginal delivery, tissues collected within 2 h of birth); they were weighed and frozen in liquid nitrogen and stored at -80°C for Northern blot analyses. In addition, sheep adrenal glands were collected from fetuses at 90 days (n = 5), 109–111 days (n = 4), 120–121 days (n = 6), 130–131 days (n = 6), and 142–143 days (n = 4). Adrenal glands were also collected from pregnant ewes (n = 17) between 109 and 143 days of gestation and from nonpregnant ewes (n = 8). Both adult and fetal adrenal glands were fixed by immersion in 0.1 M phosphate-buffered paraformaldehyde (4%) and embedded in paraffin. Sections (6 µm) were prepared and mounted on pretreated slides (Superfrost Plus; Fisher Scientific, Pittsburgh, PA) to localize AT1R and CYP11B using immunocytochemical techniques. The protocols were approved by the Committee on Animal Care at Cornell University, Ithaca, New York, and at the universities of Wisconsin-Madison and Adelaide, Australia.

Adrenal Northern Blot Analysis

The Northern blot procedure used in the present study has been fully described previously [10]. In brief, total RNA was prepared from individual adrenal glands by the guanidinium isothiocyanate-cesium chloride density gradient method. The recovery and purity of RNA were determined spectrophotometrically (260 and 280 nm). From each adrenal sample, total RNA (5 µg) was subjected to gel electrophoresis, and RNA was transferred to nylon membranes (Gene Screen; DuPont NEN, Wilmington, DE) and cross-linked to the membrane by UV radiation (Stratolinker; Stratagene, La Jolla, CA). Membranes were hybridized using a cDNA specific for the bovine AT1R (corresponding to bases 37–972 of the protein coding sequence), which was labeled by asymmetric polymerase chain reaction with [32P]dCTP as described previously [11]. Autoradiography was performed for 48 h with an intensifying screen (Cronex; DuPont NEN, Boston, MA). Membranes were stripped and then were reprobed with an 18S rRNA probe. Northern blots were quantified using scanning densitometry [10] and normalized to the content of 18S rRNA detected in each sample, and data are presented as arbitrary densitometric units of mRNA. To compare the effect of gestational age on AT1R mRNA expression, a second-order regression fit of the data was performed with 95% confidence intervals.

Adrenal Immunohistochemistry

To localize CYP11B and AT1R protein in paraffin sections (6 µm) of adrenal glands, we used the peroxidase anti-peroxidase (PAP) technique as described previously [12] with an Immunopure metal-enhanced diaminobenzidine substrate (Pierce, Rockford, IL) as the chromagen.

The AT1R-specific polyclonal antibody, obtained from Santa Cruz Biotechnology (Santa Cruz, CA), was raised in rabbits against an epitope corresponding to amino acids 306–359 of the human AT1R and has been characterized previously for the detection of the ovine AT1R [13, 14]. The CYP11B polyclonal antibody, generously provided by Professor Pieter Swart (Department of Biochemistry, University of Stellenboch, South Africa), was raised in rabbits against immunopurified ovine CYP11B enzyme [15], which detects a single band at 50 kDa on Western immunoblot analysis against sheep adrenal microsomes [16].

To determine the separation between the cells of the zona glomerulosa and zona fasciculata at the light microscope level, additional sections were stained with hematoxylin and eosin. Adrenocortical cells of the zona glomerulosa have less cytoplasm and therefore stain more intensely with hematoxylin, whereas adrenocortical cells of the zona fasciculata have more cytoplasm and therefore stain more intensely with eosin [17].


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Northern Blot Analysis

In the fetal adrenal gland, from as early as 105 days gestation, AT1R mRNA was detectable by Northern blot analysis at the expected size of 2.4 kilobases (kb) (Fig. 1). There was a 4-fold decrease in expression of AT1R mRNA between 105 days and 120–129 days, whereas AT1R mRNA levels remained relatively constant from 120–129 days to the newborn period (Fig. 2).



View larger version (19K):
[in this window]
[in a new window]
  		FIG. 1. A Northern blot analysis of AT1R mRNA in the fetal sheep adrenal gland with advancing gestational age at 105 days, 120–129 days, and 136 days and within 2 h of birth. The total cellular RNA used was 5 µg/lane. AT1R mRNA was observed at the expected size of 2.4 kb



View larger version (17K):
[in this window]
[in a new window]
  		FIG. 2. Northern blot data of AT1R mRNA in the fetal sheep adrenal gland with advancing gestational age at 105 days, 120–129 days, 136 days, and at birth (within 2 h of birth) with the data corrected for loading using 18S rRNA. Data are presented as arbitrary densitometric units of mRNA. The highest AT1R mRNA expression was observed at 105 days gestation; expression decreased significantly by around 120 days and was similar between 120 days and term. A second-order regression fit of the data was performed with 95% confidence limits. The regression was highly significant (P < 0.0005), with the equation Y = 0.012X(2) - 3.046X + 202.488 and r2 = 0.827

Localization of AT1R-ir

In the adult adrenal gland and in the fetal adrenal gland from as early as 90 days gestation, intense AT1R-ir was observed predominantly in the zona glomerulosa and to a lesser extent in the zona fasciculata (Fig. 3). In the zona fasciculata, some cells were stained more intensely for the AT1R than others, particularly those cells that were closer to the border with the adrenal medulla (Fig. 3). AT1R-ir was also detectable in the steroidogenic cells that surround the central vein (Fig. 3). In the adult and fetal adrenal gland, AT1R-ir was not detectable in the adrenal medulla (Fig. 3). The pattern of localization of AT1R-ir was very similar in the adrenal gland of fetal and adult sheep (Fig. 3).



View larger version (154K):
[in this window]
[in a new window]
  		FIG. 3. (A–H) Photomicrographs of fetal sheep adrenal glands at 90 days, 120 days, and 142 days gestation and of adult sheep adrenal glands, immunostained for AT1R-ir (brown reaction product) and counterstained with Mayer's hematoxylin. A–D) Intense immunostaining was present in the zona glomerulosa, and less intense staining was present in the zona fasciculata. In D, the thickness of the zona glomerulosa shown is due to the 10-fold increase in size between the term fetal adrenal and adult adrenal gland. E–G) Localization of AT1R-ir at the zona fasciculata/medullary border (E and G) and the adrenal medullary/central vein region (F and H) in the fetal adrenal at 90 days gestation (E and F) and in the adult sheep adrenal gland (G and H). E–G) Intense staining of AT1R in the zona fasciculata adjacent to the unstained adrenomedullary cells. Bar = 100 µm. C, Adrenal capsule; ZG, zona glomerulosa; ZF, zona fasciculata; v, central vein

Localization of CYP11B-ir

In the fetal sheep adrenal gland, from as early as 90 days gestation, CYP11B-ir was present throughout all zones of the adrenal cortex, and positive staining was also observed in the cells surrounding the central adrenal vein (Fig. 4). It is likely that the cells surrounding the adrenal vein that are CYP11B immunopositive are capable of the synthesis of steroids, as we found that they also stained positively for other enzymes in the steroidogenic pathway such as cytochrome P450 side-chain cleavage (CYP11A1), CYP17, and 3ß-hydroxysteroid dehydrogenase (3ßHSD) (data not shown).



View larger version (171K):
[in this window]
[in a new window]
  		FIG. 4. (A–L) Photomicrographs of fetal sheep adrenal glands at 90 days, 120 days, and 142 days gestation and of adult sheep adrenal glands, immunostained for CYP11B-ir (brown reaction product) and counterstained with Mayer's hematoxylin. A (90 days), D (120 days), G (142 days), and J (Adult) show the unstained capsule and the presence of intense immunostaining for CYP11B in the zona glomerulosa and in the zona fasciculata. B (90 days), E (120 days), H (142 days), and K (Adult) show the border between the zona fasciculata and the adrenal medulla (marked by arrows) where intense immunostaining for CYP11B was present in the zona fasciculata and absent from the adrenomedullary cells. C (90 days), F (120 days), I (142 days), and L (Adult) show positive staining for CYP11B in the cells that surround the adrenal vein, in contrast to the unstained adrenomedullary cells. Bar = 100 µm. C, Adrenal capsule; ZG, zona glomerulosa; ZF, zona fasciculata; v, central vein

In all adrenal glands examined, we observed no difference in the intensity of CYP11B-ir between the zona glomerulosa and the zona fasciculata. In the adult sheep adrenal, the pattern and intensity of staining for CYP11B-ir were similar to those observed in the fetal adrenal glands (Fig. 4).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
In adult and fetal sheep adrenal cells in vitro, AII administration blocks ACTH-stimulated induction of CYP17 activity and cortisol production [4, 18]. Therefore, AII may play an important role in the regulation of cortisol synthesis during fetal life [4]. In the present study, we observed that AT1R mRNA is expressed in the fetal sheep adrenal gland, and the highest level of AT1R mRNA expression was observed at 105 days gestation. The presence of AT1R-ir in the zona fasciculata and the higher levels of expression of AT1R at around 100 days gestation suggest that suppression of CYP17 observed at this stage of gestation [3] may be mediated via AT1R. We propose that with advancing gestational age, in addition to increased secretion of fetal pituitary ACTH that induces ACTH receptors in the fetal adrenal [19], it is the fall in AT1R expression that allows ACTH [19] to ultimately override AT1R-mediated inhibition of CYP17 expression in the zona fasciculata and thus allow the prepartum increase in fetal plasma cortisol concentrations [3].

In the fetus, the underlying reason for the lack of regulation of aldosterone synthesis and secretion mediated via the AT1R has not been established. In contrast to what occurs in the adult and newborn sheep, fetal plasma aldosterone concentrations do not increase in response to AII stimulation [3, 6, 7], even though we have shown previously that activation of phospholipase C does occur in fetal sheep adrenal cells in vitro [20]. In the present study we observed intense staining of AT1R-ir in the zona glomerulosa of the fetal adrenal gland. Therefore, the lack of responsiveness of the fetal adrenal to secrete aldosterone in response to AII stimulation in fetal life is not due to the absence of AT1R in the zona glomerulosa. In view of the known ability of the AT1R to couple to phospholipase C at this time [20], an alternative possibility is that AT1R signaling is blocked or altered by high coexpression of the type 2 ATR (AT2R). Such receptors are known to be present in the fetal human adrenal at high levels in midgestation [21]; but while it is known that AT2R expression is low in the adult ovine adrenal [20], comparative information in the fetal sheep has been unavailable to date. Thus, it is possible that there may be a change in relative ratios of the AT1R to AT2R in the fetal adrenal gland that mediates the change in responsiveness of the zona glomerulosa to AII after birth. A further possibility is that there is an endogenous inhibitor in the fetal adrenal gland that is blocking the AT1R signaling pathway. A blockade of the AT1R signaling pathway may impair the expression of steroidogenic acute regulatory protein (StAR), which functions to mobilize cholesterol from the outer to the inner mitochondrial membrane [22, 23]. Consistent with recent studies in the human [24], preliminary data from our laboratory indicate that StAR immunoreactivity is reduced in the zona glomerulosa of the fetal sheep adrenal compared to the adult sheep adrenal cortex [25]. Clearly, further studies will be necessary to determine the role of AII receptors in the acute activation of the synthesis and secretion of aldosterone in postnatal life.

The expression of CYP11A1, 3ßHSD, and cytochrome P450 21 hydroxylase (CYP21A2) has been demonstrated in the zona glomerulosa of the fetal sheep adrenal gland [2]. From as early as 87 days gestation in the fetal sheep adrenal gland, the final enzyme in the steroidogenic pathway required for the synthesis of aldosterone, CYP11B, has been detected [9]; however, the zonal localization has not been determined. Recently, we have shown that in the primate fetal adrenal it is not until term that CYP11B-ir is present in the definitive zone, which is the putative zona glomerulosa in the adult primate adrenal cortex [16]. The late onset of expression of CYP11B-ir in the definitive zone parallels the increase in plasma aldosterone concentrations in the late-gestation rhesus fetus [26]. In the present study, we observed no ontogenetic change in the zonal pattern of distribution or intensity of CYP11B-ir from 90 days gestation until term. In addition, the pattern of localization of CYP11B-ir was similar between the fetal and adult adrenal glands. Therefore in the fetal sheep, the developmental increase in the plasma aldosterone concentrations [3, 6] is not due to the induction of expression of CYP11B in the zona glomerulosa. Another possibility is that CYP11B activity in the zona glomerulosa is inhibited before birth. There is evidence in the adult adrenal gland that nitric oxide negatively modulates aldosterone synthesis via a direct inhibition of cytochrome P450 enzymes [27]; however, little is known about the role of nitric oxide in the developing adrenal gland. The mitochondrial inner membrane structure/composition has been demonstrated to be important for full aldosterone synthase activity [28], and ultrastructural studies in the late-gestation sheep adrenal have shown that there is an increase in the proportion of tubular cristae to lamellar cristae within the mitochondria of the zona glomerulosa [29]. Previous studies have also shown that low levels of O2 in vitro decrease basal aldosterone secretion in adult bovine zona glomerulosa cells [30] and that the O2 sensitivity of the aldosterone pathway is present throughout development [31]. The transition from fetal to neonatal life results in a dramatic increase in arterial pO2, which may lead to increased CYP11B activity and thereby play a key role in the increase in aldosterone secretion at this time.

In summary, the presence of AT1R in the zona fasciculata and the higher levels of expression of AT1R at around 100 days gestation suggest that suppression of CYP17 may be mediated via AT1R. The abundant expression of AT1R-ir and CYP11B-ir in the zona glomerulosa of the fetal sheep adrenal gland would suggest that lack of AII stimulation of aldosterone secretion is not due to an absence of AT1R or CYP11B in the zona glomerulosa.


   ACKNOWLEDGMENTS
 
The authors acknowledge Dr. Julie Owens, Department of Physiology, The University of Adelaide, for the generous contribution of fetal sheep tissues.


   FOOTNOTES
 
First decision: 21 April 1999.

1 The work was supported in part by NIH Grants HL56702 (I.M.B.) and HD21350 (P.W.N.) and by USDA 9601773 (I.M.B.), AHA-WI 95-GB-41 (I.M.B.). C.L.C. was supported by the NHMRC of Australia (990275) and a J.B. Reid Fellowship from The University of Adelaide, South Australia. Presented in part at the 8th Adrenal Cortex Conference, Orford, Quebec, 1998. Back

2 Correspondence: Catherine L. Coulter, Department of Physiology, Medical School Building, Room N411, The University of Adelaide, GPO Box 498, North Terrace, Adelaide, South Australia 5005, Australia. FAX: 61 8 8303 3356; catherine.coulter{at}adelaide.edu.au Back

Accepted: October 7, 1999.

Received: March 19, 1999.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Mesiano S, Jaffe RB. Developmental and functional biology of the primate fetal adrenal cortex. Endocr Rev 1997; 18:378–403.[Abstract/Free Full Text]
  2. Tangalakis K, Coghlan JP, Connell J, Crawford R, Darling P, Hammond VE, Haralambidis J, Penschow J, Wintour EM. Tissue distribution and levels of gene expression of three steroid hydroxylases in ovine fetal adrenal glands. Acta Endocrinol (Copenh) 1989; 120:225–232.[Medline]
  3. Wintour EM, Crawford R, McFarlane A, Moritz K, Tangalakis K. Regulation and function of the fetal adrenal gland in sheep. Endocr Res 1995; 21:81–89.[Medline]
  4. Rainey WE, Oka K, Magness RR, Mason JI. Ovine fetal adrenal synthesis of cortisol: regulation by adrenocorticotropin, angiotensin II and transforming growth factor-beta. Endocrinology 1991; 129:1784–1790.[Abstract]
  5. Aguilera G, Kiss A, Lu A, Camacho C. Regulation of adrenal steroidogenesis during chronic stress. Endocr Res 1996; 22:433–443.[Medline]
  6. Wintour EM, Brown EH, Denton DA, Hardy KJ, McDougall JG, Oddie CJ, Whipp GT. The ontogeny and regulation of corticosteroid secretion by the ovine fetal adrenal. Acta Endocrinol (Copenh) 1975; 79:301–316.[Medline]
  7. Siegel S, Fisher DA. Ontogeny of the renin-angiotensin-aldosterone system in the fetal and newborn lamb. Pediatr Res 1980; 14:99–102.[Medline]
  8. Boon WC, Roche PJ, Butkus A, McDougall JG, Jeyaseelan K, Coghlan JP. Functional and expression analysis of ovine steroid 11 beta-hydroxylase (cytochrome P450 11 beta). Endocr Res 1997; 23:325–347.[Medline]
  9. John ME, Simpson ER, Carr BR, Magness RR, Rosenfeld CR, Waterman MR, Mason JI. Ontogeny of adrenal steroid hydroxylase: evidence for cAMP-independent gene expression. Mol Cell Endocrinol 1987; 50:263–268.[CrossRef][Medline]
  10. Myers DA, McDonald TJ, Nathanielsz PW. Effect of placement of dexamethasone adjacent to the ovine fetal paraventricular nucleus on adrenocortical steroid hydroxylase messenger ribonucleic acid. Endocrinology 1992; 131:1329–1335.[Abstract]
  11. Bird IM, Mason JI, Rainey WE. Regulation of type 1 angiotensin II receptor messenger ribonucleic acid expression in human adrenocortical carcinoma H295 cells. Endocrinology 1994; 134:2468–2474.[Abstract]
  12. Coulter CL, Read LC, Carr BR, Tarantal AF, Barry S, Styne DM. A role for epidermal growth factor in the morphological and functional maturation of the adrenal gland in the fetal rhesus monkey in vivo. J Clin Endocrinol Metab 1996; 81:1254–1260.[Abstract]
  13. Bird IM, Zheng J, Corbin CJ, Magness RR, Conley AJ. Immunohistochemical analysis of AT1 receptor versus P450c17 and 3 beta HSD expression in ovine adrenals. Endocr Res 1996; 22:349–353.[Medline]
  14. Bird IM, Zheng J, Cale JM, Magness RR. Pregnancy induces an increase in angiotensin II type-1 receptor expression in uterine but not systemic artery endothelium. Endocrinology 1997; 138:490–498.[Abstract/Free Full Text]
  15. Bellstedt DU, Louv RP, Parringer BA, Werder N, VanderMerwe KJ, Swart P. Antibody production to adrenal cytochrome P450-dependent enzymes using acid-treated bacteria as immune carriers. Biochem Soc Trans 1993; 21:414S.
  16. Coulter CL, Jaffe RB. Functional maturation of the primate fetal adrenal in vivo: 3. Specific zonal localization and developmental regulation of CYP21A2 (P450c21) and CYP11B1/CYP11B2 (P450c11/aldosterone synthase) lead to integrated concept of zonal and temporal steroid biosynthesis. Endocrinology 1998; 139:5144–5150.[Abstract/Free Full Text]
  17. Robinson PM, Rowe EJ, Wintour EM. The histogenesis of the adrenal cortex in the foetal sheep. Acta Endocrinol (Copenh) 1979; 91:134–149.[Medline]
  18. Bird IM, Magness RR, Mason JI, Rainey WE. Angiotensin-II acts via the type 1 receptor to inhibit 17 alpha-hydroxylase cytochrome P450 expression in ovine adrenocortical cells. Endocrinology 1992; 130:3113–3121.[Abstract]
  19. Saez JM, Durand P, Cathiard AM. Ontogeny of the ACTH receptor, adenylate cyclase and steroidogenesis in adrenal. Mol Cell Endocrinol 1984; 38:93–102.[Medline]
  20. Bird IM, Mason JI, Rainey WE. Hormonal regulation of angiotensin II type 1 receptor expression and AT1-R mRNA in human adrenocortical cells. Endocr Res 1996; 21:169–182.
  21. Breault L, Lehoux JG, Gallo-Payet N. Angiotensin II receptors in the human adrenal gland. Endocr Res 1996; 22:355–361.[Medline]
  22. Clark BJ, Wells J, King SR, Stocco DM. The purification, cloning, and expression of a novel LH-induced mitochondrial protein in MA-10 mouse leydig tumor cells: characterization of the steroidogenic acute regulatory protein (StAR). J Biol Chem 1994; 269:28314–28322.[Abstract/Free Full Text]
  23. Kim YC, Ariyoshi N, Artemenko I, Elliot ME, Bhattacharyya KK, Jefcoate CR. Control of cholesterol access to cytochrome P450scc in rat adrenal cells mediated by regulation of the steroidogenic acute regulatory protein. Steroids 1997; 62:10–20.[CrossRef][Medline]
  24. Pollack SE, Furth EE, Kallen CB, Arakane F, Kiriakidou M, Kozarsky KF, Strauss III JF. Localization of the steroidogenic acute regulatory protein in human tissues. J Clin Endocrinol Metab 1997; 82:4243–4251.[Abstract/Free Full Text]
  25. Coulter CL, Bird IM. Ontogeny of the zonal expression of steroidogenic acute regulatory protein (StAR) and cytochrome P450C11 (CYP11B) in the sheep adrenal. In: The Program of the 81st Meeting of the Endocrine Society; 1999; San Diego, CA. P3-450.
  26. Jaffe RB, Mulchahey JJ, Di Blasio AM, Martin MC, Blumenfeld Z, Dumesic DA. Peptide regulation of pituitary and target tissue function and growth in the primate fetus. Recent Prog Horm Res 1988; 44:431–549.
  27. Hanke CJ, Drewett JG, Myers CR, Campbell WB. Nitric oxide inhibits aldosterone synthesis by a guanylyl cyclase-independent effect. Endocrinology 1998; 139:4053–4060.[Abstract/Free Full Text]
  28. Yanagibashi K, Haniu M, Shively JE, Shen WH, Hall P. The synthesis of aldosterone by the adrenal cortex. Two zones (fasciculata and glomerulosa) possess one enzyme for 11 beta-, 18-hydroxylation, and aldehyde synthesis. J Biol Chem 1986; 261:3556–3562.[Abstract/Free Full Text]
  29. Webb PD. Development of the adrenal cortex in the fetal sheep: an ultrastructural study. J Dev Physiol 1980; 2:161–181.[Medline]
  30. Raff H, Ball DL, Goodfriend TL. Low oxygen selectively inhibits aldosterone secretion from bovine adrenocortical cells in vitro. Am J Physiol 1989; 256:E640–644.
  31. Papanek PE, Jankowski BM, Raff H. Aldosterone release from adrenal cells is inhibited by reduced oxygen levels in vitro during maturation in rabbits. Reprod Fertil Dev 1996; 8:1131–1136.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
A. J. W. Fletcher, X. H. Ma, W. X. Wu, P. W. Nathanielsz, H. H. G. McGarrigle, A. L. Fowden, and D. A. Giussani
Antenatal glucocorticoids reset the level of baseline and hypoxemia-induced pituitary-adrenal activity in the sheep fetus during late gestation
Am J Physiol Endocrinol Metab, February 1, 2004; 286(2): E311 - E319.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. Chamoux, A. Narcy, J.-G. Lehoux, and N. Gallo-Payet
Fibronectin, Laminin, and Collagen IV as Modulators of Cell Behavior during Adrenal Gland Development in the Human Fetus
J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1819 - 1828.
[Abstract] [Full Text] [PDF]

Home page
 Reproductive SciencesHome page
E. Zambrano, P. W. Nathanielsz, and T. J. McDonald
Prenatal and Postnatal Ovine Adrenal Cell responses to Prostaglandin E2
Reproductive Sciences, May 1, 2001; 8(3): 149 - 157.
[Abstract] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Coulter, C. L.
Right arrow Articles by Bird, I. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Coulter, C. L.
Right arrow Articles by Bird, I. M.
Agricola
Right arrow Articles by Coulter, C. L.
Right arrow Articles by Bird, I. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS