help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berg, M. N.
Right arrow Articles by Waddell, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berg, M. N.
Right arrow Articles by Waddell, B. J.
Endocrinology Vol. 143, No. 1 222-227
Copyright © 2002 by The Endocrine Society

REPRODUCTION-DEVELOPMENT

Glucocorticoids and Progesterone Prevent Apoptosis in the Lactating Rat Mammary Gland

Melissa N. Berg, Arun M. Dharmarajan and Brendan J. Waddell

Department of Anatomy and Human Biology, The University of Western Australia, Crawley, Perth, Western Australia 6009

Address all correspondence and requests for reprints to: Dr. Brendan Waddell, Department of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, Perth, Western Australia 6009. E-mail: bwaddell{at}anhb.uwa.edu.au


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Apoptosis, a form of noninflammatory cell death, plays a central role in mammary gland involution after weaning. Previous studies have shown that apoptosis in the postweaning mammary gland is substantially reduced by treatment with glucocorticoids or progesterone, but whether these steroids exert a similar antiapoptotic effect during normal lactation is not known. Therefore, the present study used an in vivo rat model to assess the effects of progesterone and glucocorticoids on apoptosis in the lactating mammary gland. Rats were untreated, sham operated, ovariectomized (OVX), and/or adrenalectomized (ADX) on d 10 of lactation. Additional groups of OVX/ADX rats were treated with either progesterone or corticosterone. Mammary gland apoptosis was determined 3 d later by 3'-end labeling of fragmented DNA and by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling analysis (TUNEL). DNA fragmentation was relatively low in the mammary gland from untreated and sham-operated rats and was unaffected by either ADX or OVX alone. In contrast, DNA fragmentation was markedly elevated in OVX/ADX rats (P < 0.01), but this effect on mammary gland apoptosis was prevented by replacement with either corticosterone or progesterone. Consistent with these data, dying cells identified by TUNEL analysis were readily observed in the alveolar epithelium of mammary tissue from OVX/ADX rats but not in any of the other groups. These data demonstrate that during normal lactation, mammary gland apoptosis is inhibited by endogenous progesterone and glucocorticoids. Importantly, the presence of either steroid alone was sufficient to prevent apoptosis, suggesting that their antiapoptotic effects in the lactating mammary gland may be mediated via similar signaling pathways.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
APOPTOSIS IS A form of noninflammatory, programmed cell death and plays a central role in mammary gland involution after weaning (1, 2, 3). The mammary epithelium terminally differentiates in pregnancy, becomes fully functional under the influence of lactogenic hormones, and as such is committed to apoptosis after weaning as part of the involution process (4). Several factors may play a role in apoptosis induction during involution, including falls in the levels of systemic hormones, such as glucocorticoids, and local modulators of lactation (5) including the physical effects of milk engorgement (6). Feng et al. (7) have shown that during the postweaning period, glucocorticoid replacement reduces the extent of mammary gland apoptosis, but it is not clear whether this antiapoptotic effect also occurs in the presence of the suckling stimulus. Such an antiapoptotic action of glucocorticoids during lactation would be additional to their well-recognized role as stimulators of milk protein synthesis (8). Progesterone administration also reduces apoptosis in the postweaning mammary gland (7), but it is not clear whether progesterone is antiapoptotic in the lactating mammary gland. Indeed, it is unclear what role progesterone plays in supporting mammary gland function in lactation (8). This is despite plasma progesterone levels during lactation in the rat being comparable to maximal levels in pregnancy (9). Therefore, the present study examined the possibility that progesterone and glucocorticoids both serve to limit mammary gland apoptosis during lactation. This involved measurement of mammary gland apoptosis by both 3'-end labeling and in situ analysis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling [TUNEL]) after removal of endogenous progesterone (by ovariectomy) and/or glucocorticoids (by adrenalectomy).


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Reagents and animals
Corticosterone, progesterone, and bovine {gamma}-globulin were obtained from Sigma (St. Louis, MO). Corticosterone antiserum (B3-163) was obtained from Endocrine Sciences, Inc. Products (Calabasas, CA). [1,2,6,7-3H]Corticosterone and [{alpha}-32P]dideoxy-ATP were obtained from Amersham Pharmacia Biotech Australia (Sydney, Australia).

Mature nulliparous Wistar rats were obtained from the Animal Resource Center (Murdoch, Australia) and housed as previously described (10). Rats were mated overnight and the morning on which a cervical plug was found was designated as d 1 of pregnancy. In this colony parturition usually occurs in the morning of d 23. Pregnant rats were transferred to separate cages 3–4 d before expected delivery, and the day of delivery was designated d 0 of lactation. All litters were standardized to 10 pups within 3 d of birth. All procedures involving animals were conducted after approval by the Animal Ethics Committee of The University of Western Australia.

Experimental groups
Mammary gland apoptosis was assessed at d 13 of lactation in control, sham-operated, and 5 treated groups of rats (total of 7 groups, n = 5–6 each). Treatments involved adrenalectomy and/or ovariectomy (11), with or without steroid replacement. Specifically, adrenalectomy was performed at d 10 of lactation to remove endogenous corticosterone (ADX group). To reduce endogenous progesterone, rats were either ovariectomized (OVX) or ovariectomized and adrenalectomized (OVX/ADX) at d 10 of lactation. Two additional OVX/ADX groups received replacement of either progesterone (twice daily, 0.3-ml sc injections of 10 mg/ml progesterone in peanut oil) or corticosterone (100 µg/ml of corticosterone administered in drinking water) over d 10–13 of lactation.

Surgical interventions
Ovariectomy and/or adrenalectomy were performed via two dorsolateral incisions under halothane/nitrous oxide anesthesia in the morning of d 10 of lactation (11). Pups were placed on a warming pad when separated from their mothers (maximum time of separation was 45 min). Saline (0.9% NaCl wt/vol) was provided to all ADX and OVX/ADX rats for drinking ad libitum. Ovariectomy and adrenalectomy was also carried out in two additional female rats that were implanted with chronic carotid cannulas for subsequent blood sampling as previously described (11). These rats received corticosterone in drinking water as described above, and 72 h later blood samples (~0.2 ml each) were obtained via the cannula at 3-h intervals for 24 h. These rats were briefly anesthetized with halothane/nitrous oxide for blood collection, and the cannula was flushed with heparinized saline (20 IU/ml) after each sample.

Tissue collection and fixation
Mammary tissue from the three left inguinal glands was collected on the morning of d 13 of lactation (72 h after surgery) and a portion was snap frozen and stored at -70 C until DNA extraction and subsequent analysis of DNA fragmentation (12). A portion of mammary tissue was also immersed in 4% paraformaldehyde in PBS pH 7.4 (13.6 mM NaCl, 2.7 mM KCl, 10.1 mM Na2HPO4, and 1.8 mM KH2PO4), rotated at 4 C for 16–20 h, and then processed for routine paraffin histology. In addition, blood was collected from the dorsal aorta, centrifuged at 13,000 x g for 5 min, and plasma collected and stored at -20 C until analysis of corticosterone and progesterone concentrations.

Hormone analysis
Plasma progesterone concentrations were determined using a commercial RIA kit (Coat-a-Count, Diagnostic Products Corp., Los Angeles, CA), and plasma corticosterone levels were determined by RIA as previously described (10, 13). Briefly, samples were diluted in assay buffer (0.9% (wt/vol) NaCl, 0.01% bovine {gamma}-globulin, 0.01% sodium azide), heat inactivated at 65–70 C for 30 min to remove corticosteroid binding globulin activity, and then incubated at 4 C for 2 h with [3H]corticosterone and corticosterone antiserum (final dilution 1:128,000). Free and bound steroids were separated by incubation with 0.25% charcoal at 4 C for 10 min and radioactivity determined by liquid scintillation spectrophotometry.

Extraction and analysis of DNA for internucleosomal cleavage
Genomic DNA was extracted from mammary tissue as previously described (12, 14). Briefly, the tissue was homogenized and protein extracted by a series of phenol/chloroform/isoamylalcohol extractions. The concentration of DNA was determined by spectrophotometry, and 1 µg DNA from each sample was labeled on 3'-ends with [{alpha}-32P]dideoxy-ATP (3000 Ci/mmol) using the terminal transferase reaction previously described (12, 14). DNA fragments of radiolabeled samples were separated on 2% agarose gels in TAE buffer (Tris-acetate/EDTA) for 3 h at 60 V. The gels were dried for 2 h without heat and exposed to X-Omat films (Kodak, Rochester, NY) for 48 h at -70 C. The extent of internucleosomal DNA fragmentation was measured by the incorporation of [{alpha}-32P]dideoxy-ATP onto the 3'-ends of low molecular weight (<20 kB) fragments. This was quantified by excising lowmolecular-weight bands and measuring emissions by liquid scintillation spectrophotometry.

In situ cell death detection using the TUNEL assay
Cell death was localized in tissue sections by TUNEL analysis (15). Paraffin tissue sections (4 µm) were dewaxed by incubation at 60 C for 30 min and washed twice for 5 min in toluene. Sections were hydrated through a graded series of ethanol and PBS and then incubated with proteinase K (20 µg/ml in PBS) for 30 min at 37 C. Thereafter, an Apoptag Plus Peroxidase in situ apoptosis detection kit (Intergen Discovery Products, Purchase, NY) was used for nick-end labeling according to the manufacturer’s instructions. Nuclei with DNA cleavage were visualized with DAB (3,3'-diaminobenzidine tetrahydrochloride) and sections were counterstained with methyl green. Postweaning mammary tissue was included as a positive control.

Statistical analysis
Treatment effects on plasma steroid concentrations and DNA fragmentation were assessed by one-way ANOVA. When the F test was significant (P < 0.05), specific between-group differences were assessed by least significant differences (LSD) tests.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Plasma steroid concentrations
Plasma progesterone concentrations on d 13 were dramatically reduced by ovariectomy 3 d earlier (Fig. 1Go) and were even lower (P = 0.02, unpaired t test, see inset in Fig. 1Go) in the OVX/ADX group. Progesterone replacement to OVX/ADX rats raised plasma levels to about 50% of sham-operated animals. Plasma corticosterone concentrations on d 13 of lactation were almost negligible following adrenalectomy on d 10 (Fig. 2), and were partially restored (P < 0.05) in rats administered corticosterone in drinking water (see inset in Fig. 2Go). To assess whether the relatively low levels of plasma corticosterone observed after corticosterone replacement were owing to rats drinking only in the dark phase of the light cycle, plasma corticosterone levels were measured in samples obtained from two additional OVX/ADX rats at 3-h intervals over a 24-h period during corticosterone replacement. Plasma corticosterone levels were again very low in these animals at 1000 h (11 and 5 ng/ml, respectively) but reached maximal levels of 85 and 96 ng/ml, respectively, during the dark phase of the light cycle.



View larger version (46K):
[in this window]
[in a new window]
  		Figure 1. Plasma progesterone concentrations on d 13 of lactation in control, sham, OVX, ADX, and OVX/ADX rats with or without corticosterone (Cort) or progesterone (P4) replacement. Values are the mean ± SEM. There was significant variation among means (P < 0.001, one-way ANOVA) and for specific group comparisons, those values without common notations (a, b, or c) differ significantly (P < 0.05, LSD test). Inset shows plasma progesterone concentrations on a reduced scale for OVX and OVX/ADX groups (*, P = 0.02, compared with OVX group, unpaired t test).

 


View larger version (45K):
[in this window]
[in a new window]
  		Figure 2. Plasma corticosterone concentrations on d 13 of lactation in control, sham, OVX, ADX, and OVX/ADX rats with or without corticosterone (Cort) or progesterone (P4) replacement. Values are the mean ± SEM. There was significant variation among means (P < 0.001, one-way ANOVA) and for specific group comparisons, those values without common notations (a or b) differ significantly (P < 0.001, LSD test). Inset shows plasma corticosterone concentrations on a reduced scale for ADX and OVX/ADX ± corticosterone replacement groups (*, P < 0.05, compared with the ADX and OVX/ADX groups, one-way ANOVA, and LSD test).

 
Quantitation of DNA fragmentation by 3'-end labeling
DNA fragmentation into 180-bp multiples was clearly evident in mammary tissue from 2-d postweaning and OVX/ADX rats but not in tissue from control, sham-operated, OVX or ADX rats (Fig. 3AGo). In contrast, mammary tissue from OVX/ADX rats showed a high level of DNA fragmentation, but this was not evident in OVX/ADX rats given either progesterone or corticosterone replacement. This overall pattern of DNA fragmentation was confirmed by quantitative analysis of 3'-end-labeled low-molecular-weight DNA fragments, which showed clearly elevated fragmentation in the OVX/ADX rats, compared with all other groups (P < 0.01; Fig. 3BGo).



View larger version (47K):
[in this window]
[in a new window]
  		Figure 3. DNA fragmentation in mammary on d 13 of lactation in control, sham, OVX, ADX, and OVX/ADX rats with or without corticosterone (Cort) or progesterone (P4) replacement. A shows a representative autoradiograph of 3'-end DNA labeling, including a 2-d postweaning mammary gland as a positive control, and B shows quantitation of DNA fragmentation. Values are mean ± SEM. Those values without common notations (a or b) differ significantly (P < 0.01, one-way ANOVA and LSD test).

 
In situ cell death detection by TUNEL analysis
Dying cells identified by TUNEL analysis were rarely observed in sections of mammary tissue from control (Fig. 4AGo), sham-operated, OVX, and ADX rats. In contrast, TUNEL-positive cells were readily apparent in the alveolar epithelium of mammary tissue from OVX/ADX rats (Fig. 4BGo), comparable to that observed in the postweaning mammary gland (not shown). Administration of either corticosterone or progesterone to OVX/ADX rats, however, prevented this increase in alveolar epithelial cell death (Fig. 4Go, C and D).



View larger version (127K):
[in this window]
[in a new window]
  		Figure 4. TUNEL analysis of rat mammary gland sections from control lactating (A), OVX/ADX lactating (B), OVX/ADX lactating with corticosterone replacement (C), and OVX/ADX lactating with progesterone replacement (D). Examples of TUNEL-positive cells are arrowed. Scale bars, 200 µm.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
This study investigated the role of glucocorticoids and progesterone in the prevention of apoptosis in the rat mammary gland during lactation. Removal of both glucocorticoids and progesterone by concurrent ovariectomy and adrenalectomy was shown to induce apoptosis, primarily in the secretory epithelium, but this effect was reversed after replacement of either progesterone or corticosterone alone. These findings demonstrate that corticosterone and progesterone suppress mammary gland apoptosis in the presence of the normal suckling stimulus during lactation. Moreover, our data indicate that either steroid alone is sufficient to exert an antiapoptotic effect in the lactating mammary gland.

Inhibition of apoptosis in the lactating mammary gland by either progesterone or glucocorticoids is consistent with previous reports showing that either steroid was sufficient to inhibit apoptosis in the postweaning mammary gland (7). But these antiapoptotic steroid effects are complicated by the absence of the suckling stimulus in the postweaning period and the associated milk stasis, which in itself has been shown to induce apoptosis even in the presence of normal systemic lactogenic hormone support (16). Our observations show that glucocorticoids and progesterone are important physiological inhibitors of apoptosis in the presence of the normal suckling stimulus.

Although it is well recognized that glucocorticoids promote lactogenesis and the maintenance of lactation by stimulation of milk protein synthesis (8), the present study demonstrates that, in addition, glucocorticoids support lactation via an antiapoptotic mechanism. Interestingly, this effect of glucocorticoids is contrary to their well-recognized proapoptotic effects in the immune system (17). Progesterone is also known to provide an important stimulus for mammary gland development during pregnancy, but the periparturient decline in progesterone provides an important stimulus to lactogenesis (8). Thereafter, plasma progesterone concentrations gradually increase owing to the corpora lutea of lactation, reaching a maximum of more than 100 ng/ml on d 12 of lactation (9), comparable to maximal levels observed during pregnancy. Our results suggest that inhibition of mammary gland apoptosis may be a key role for this progesterone in lactation.

Although corticosterone replacement in OVX/ADX rats clearly prevented apoptosis, plasma corticosterone in these animals was only marginally elevated, compared with untreated OVX/ADX rats. Although this may indicate that apoptosis prevention requires only minimal corticosterone, it is more likely that plasma levels were considerably higher during the dark phase, when rats are most active and drinking, than at the time of sample collection (i.e., midmorning). This is supported by our observation that in chronically cannulated OVX/ADX rats given corticosterone replacement via drinking water, plasma corticosterone levels were very low (<20 ng/ml) throughout the day but peaked at relatively high levels (>80 ng/ml) during the dark phase of the light cycle. These observations are consistent with previous studies showing that corticosterone in drinking water elevates plasma corticosterone levels in ADX rats only during the active phase and thus partly mimics the normal physiological circadian rhythm (18).

Progesterone replacement also effectively prevented apoptosis in OVX/ADX rats, even though plasma levels reached only around 50% of those in control animals. Interestingly, plasma progesterone concentrations were significantly lower in OVX/ADX rats, compared with OVX rats, indicative of adrenocortical progesterone secretion during lactation. This extends previous observations in the pregnant rat, in which adrenals were shown to secrete a substantial proportion of circulating progesterone, particularly under conditions of stress (11).

The mechanism/s by which progesterone and glucocorticoids inhibit apoptosis during lactation are unknown, but both steroids may act via the GR. Recent studies in the rat corpus luteum show that progesterone and glucocorticoids both suppress 20{alpha}-hydroxysteroid dehydogenase expression via the GR (19), consistent with previous reports showing progesterone binding to the GR (20). Alternatively, progesterone may act via its own receptor (PR), but there is some uncertainty as to whether the PR is expressed in the rat mammary gland during lactation (21). Regardless of which specific receptor is involved, activation of either GR or PR may prevent mammary gland apoptosis by functional inhibition of proapoptotic transcription factors including AP-1. Feng et al. (7) previously demonstrated that dexamethasone inhibits the expression of AP-1-dependent genes in the postweaning mammary gland and proposed this as one of the mechanisms for the antiapoptotic effect of dexamethasone. Whether this pathway mediates the effects of glucocorticoids and progesterone in the lactating mammary gland awaits further study.

In conclusion, apoptosis was induced in the lactating mammary gland after removal of both glucocorticoids and progesterone, but the presence of either steroid alone prevented this effect. Accordingly, replacement with either glucocorticoid or progesterone alone in ADX and OVX lactating rats prevented the induction of mammary gland apoptosis. Our data show that either steroid alone is sufficient to prevent apoptosis in the lactating mammary gland and thus suggest a degree of redundancy in the mechanisms of steroid support for lactation.


   Acknowledgments
 
The authors are grateful to Mr. Steve Parkinson for technical assistance and Mr. Tony Felton for expert animal care.


   Footnotes
 
This study was supported by the Raine Medical Research Foundation (to A.M.D.), The Australian Research Council (to A.M.D. and B.J.W.), and National Health and Medical Research Council of Australia (to B.J.W.). M.N.B. supported by a University of Western Australia Postgraduate Scholarship and a Richard Walter Gibbon Supplementary Scholarship (UWA).

Abbreviations: ADX, Adrenalectomized; LSD, least significant differences; OVX, ovariectomized; OVX/ADX, ovariectomized and adrenalectomized; TUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling.

Received May 15, 2001.

Accepted for publication September 19, 2001.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Walker NI, Bennett RE, Kerr JF 1989 Cell death by apoptosis during involution of the lactating breast in mice and rats. Am J Anat 185:19–32[CrossRef][Medline]
  2. Bielke W, Ke G, Strange R, Friis R 1995 Apoptosis in mammary gland involution: isolation and characterization of apoptosis-specific genes. In: Wilde CJ, Peaker M, Knight CH, eds. Intercellular signalling in the mammary gland. New York: Plenum Press; 45–55
  3. Strange R, Friis RR, Bemis LT, Geske FJ 1995 Programmed cell death during mammary gland involution. Methods Cell Biol 46:355–368[Medline]
  4. Ossowski L, Biegel D, Reich E 1979 Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Cell 16:929–940[CrossRef][Medline]
  5. Knight CH, Peaker M, Wilde CJ 1998 Local control of mammary development and function. Rev Reprod 3:104–112[Abstract]
  6. Marti A, Jaggi R, Vallan C, Ritter PM, Baltzer A, Srinivasan A, Dharmarajan AM, Friis RR 1999 Physiological apoptosis in hormone-dependent tissues: involvement of caspases. Cell Death Differ 6:1190–1200[CrossRef][Medline]
  7. Feng Z, Marti A, Jehn B, Altermatt HJ, Chicaiza G, Jaggi R 1995 Glucocorticoid and progesterone inhibit involution and programmed cell death in the mouse mammary gland. J Cell Biol 131:1095–1103[Abstract/Free Full Text]
  8. Tucker HA 1994 Lactation and its hormonal control. In: Knobil E, Neill J, Ewing LL, Greenwald GS, Markert GL, Pfaff DW, eds. The physiology of reproduction. New York: Raven Press Ltd.; vol 2:2235–2263
  9. Taya K, Greenwald GS 1982 Peripheral blood and ovarian levels of sex steroids in the lactating rat. Endocrinol Jpn 29:453–459[Medline]
  10. Atkinson HC, Waddell BJ 1995 The hypothalamic-pituitary-adrenal axis in rat pregnancy and lactation: circadian variation and interrelationship of plasma adrenocorticotropin and corticosterone. Endocrinology 136:512–520[Abstract]
  11. Bruce NW, Willcox DL, Meyer GT, Waddell BJ 1984 Effects of handling, anaesthesia, ovariectomy and adrenalectomy on serial measurements of plasma progesterone in 16-day pregnant rats. J Endocrinol 100:189–193[Abstract/Free Full Text]
  12. Dharmarajan AM, Goodman SB, Tilly KI, Tilly JL 1994 Apoptosis during functional corpus luteum regression: evidence of a role for chorionic gonadotropin in promoting luteal cell survival. Endocr J 2:295–303
  13. Waddell BJ, Burton PJ 1993 Release of bioactive ACTH by perifused human placenta at early and late gestation. J Endocrinol 136:345–353[Abstract/Free Full Text]
  14. Tilly JL, Hsueh AJ 1993 Microscale autoradiographic method for the qualitative and quantitative analysis of apoptotic DNA fragmentation. J Cell Physiol 154:519–526[CrossRef][Medline]
  15. Waddell BJ, Hisheh S, Dharmarajan AM, Burton PJ 2000 Apoptosis in rat placenta is zone-dependent and stimulated by glucocorticoids. Biol Reprod 63:1913–1917[Abstract/Free Full Text]
  16. Marti A, Feng Z, Altermatt HJ, Jaggi R 1997 Milk accumulation triggers apoptosis of mammary epithelial cells. Eur J Cell Biol 73:158–165[Medline]
  17. Cidlowski JA, King KL, Evans-Storms RB, Montague JW, Bortner CD, Hughes Jr FM 1996 The biochemistry and molecular biology of glucocorticoid-induced apoptosis in the immune system. Recent Prog Horm Res 51:457–490
  18. Akana SF, Cascio CS, Shinsako J, Dallman MF 1985 Corticosterone: narrow range required for normal body and thymus weight and ACTH. Am J Physiol 249:R527–R532
  19. Sugino N, Telleria CM, Gibori G 1997 Progesterone inhibits 20{alpha}-hydroxysteroid dehydrogenase expression in the rat corpus luteum through the glucocorticoid receptor. Endocrinology 138:4497–4500[Abstract/Free Full Text]
  20. Maki M, Hirose M, Chiba H 1980 Occurrence of common binding sites for progestin and glucocorticoid in the lactating mammary gland of the rat. J Biochem (Tokyo) 88:1845–1854[Abstract/Free Full Text]
  21. Quirk SJ, Gannell JE, Funder JW 1984 Oestrogen administration induces progesterone receptors in lactating rat mammary gland. J Steroid Biochem 20:803–806[CrossRef][Medline]



This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
L. Rocha-Viegas, G. P. Vicent, J. L. Baranao, M. Beato, and A. Pecci
Glucocorticoids Repress bcl-X Expression in Lymphoid Cells by Recruiting STAT5B to the P4 Promoter
J. Biol. Chem., November 10, 2006; 281(45): 33959 - 33970.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Candolfi, G. Jaita, V. Zaldivar, S. Zarate, L. Ferrari, D. Pisera, M. G. Castro, and A. Seilicovich
Progesterone Antagonizes the Permissive Action of Estradiol on Tumor Necrosis Factor-{alpha}-Induced Apoptosis of Anterior Pituitary Cells
Endocrinology, February 1, 2005; 146(2): 736 - 743.
[Abstract] [Full Text] [PDF]

Home page
 J DAIRY SCIHome page
R. R. Grummer and R. R. Rastani
Why Reevaluate Dry Period Length?
J Dairy Sci, July 1, 2004; 87(13_suppl): E77 - 85.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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 Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berg, M. N.
Right arrow Articles by Waddell, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berg, M. N.
Right arrow Articles by Waddell, B. J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals