Ovariectomy enhances the expression and nuclear translocation of annexin 5 in rat anterior pituitary gonadotrophs

Kawaminami, Mitsumori; Yamaguchi, Kensei; Miyagawa, S.; Numazawa, Satoshi; Ioka, Hiroki; Kurusu, Shiro; Hashimoto, Itaru

doi:10.1016/s0303-7207(98)00091-4

Cited by 20 publications

(26 citation statements)

References 29 publications

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“…Annexin A5 was shown to locate on the nucleus in the involuting mammary epithelial cells. We have observed this kind of nuclear distribution for annexin A5 in the castration cells of the pituitary gland after ovariectomy [10]. These results suggest that annexin A5 has a nuclear function.…”

Section: Discussionsupporting

confidence: 63%

Immunohistochemical Localization of Annexin A5 in the Mammary Gland of Rats: Up-Regulation of Expression by Pup Removal

Rieanrakwong

Yonezawa

Kurusu

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. The distribution of annexin A5, a cytosolic protein related to gonadotropin releasing hormone action, was examined in the mammary gland of rats by immunohistochemistry with special reference to changes by lactation. Annexin A5 was observed in the interstitial tissues but not alveolar cells in virgin rats, while mammary epithelial cells became positive for annexin A5 in pregnant rats. The intensity of annexin A5 was decreased in lactating rats and dramatically increased after weaning, especially on the nucleus. When pups were removed from their dam at mid-lactation (day 10), annexin A5 was also increased on day 12. Apoptotic epithelial cells detected by terminal deoxynucleotidyl transferase nick end labeling were simultaneously increased. Annexin A5 mRNA expression of mammary tissues was increased after pup removal. These results are the first to demonstrate the distribution of annexin A5 in the mammary glands of lactating rats, and the enhanced expression in mammary epithelial cells after lactation suggests its involvement in mammary epithelial cell involution.KEY WORDS: annexin A5, mammary gland, mammary involution.

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Section: Discussionsupporting

confidence: 63%

Immunohistochemical Localization of Annexin A5 in the Mammary Gland of Rats: Up-Regulation of Expression by Pup Removal

Rieanrakwong

Yonezawa

Kurusu

et al. 2010

The Journal of Veterinary Medical Science

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“…This event could potentially explain the presence of structural proteins pulled down in our results. Interestingly, E2 can also modulate the expression of members of the annexin family (42,43), further supporting interplay between annexins and estrogen receptors. Taken together, these results suggest that protective aspects of E2 signaling could be mediated through estrogen receptor-ANXA interactions demonstrated here and in other reports (12,44,45), and unique to this study is an age-related change in some of these associations with ER␤.…”

Section: Discussionmentioning

confidence: 87%

Age-dependent Effects of 17β-estradiol on the Dynamics of Estrogen Receptor β (ERβ) Protein–Protein Interactions in the Ventral Hippocampus

Mott

Pinceti

Rao

et al. 2014

Molecular & Cellular Proteomics

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Recent clinical evidence suggests that the neuroprotective and beneficial effects of hormone therapy may be limited by factors related to age and reproductive status. The patient's age and length of time without circulating ovarian hormones are likely to be key factors in the specific neurological outcomes of hormone therapy. However, the mechanisms underlying age-related changes in hormone efficacy have not been determined. We hypothesized that there are intrinsic changes in estrogen receptor ␤ (ER␤) function that determine its ability to mediate the actions of 17␤-estradiol (E2) in brain regions such as the ventral hippocampus. In this study, we identified and quantified a subset of ER␤ protein interactions in the ventral hippocampus that were significantly altered by E2 replacement in young and aged animals, using two-dimensional differential gel electrophoresis coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry. This study demonstrates quantitative changes in ER␤ protein-protein interactions with E2 replacement that are dependent upon age in the ventral hippocampus and how these changes could alter processes such as transcriptional regulation. Thus, our data provide evidence that changes in ER␤ protein interactions are a potential mechanism for age-related changes in E2 responsiveness in the brain after menopause. Molecular & Cellular Proteomics 13: 10.1074/mcp.M113.031559, 760-779, 2014.The neuroprotective and beneficial effects of estrogens in the brain have been reported for decades, yet recent evidence from clinical trials suggests that the benefits of estrogens in postmenopausal women might not outweigh the risks (1-3). Specifically, the risk of cardiovascular disease and invasive breast cancer was significantly increased in postmenopausal women given hormone therapy as part of the largest clinical trial performed to date (Women's Health Initiative). These results sharply contradicted substantial evidence from numerous studies in animal models, prompting a reevaluation of the data from the Women's Health Initiative studies. Later it was determined that factors contributing to the observed detrimental effects of hormone therapy in the Women's Health Initiative study included advanced age, the types of synthetic estrogens and progestins used in the study, and, perhaps most important, the number of years postmenopause prior to the initiation of hormone therapy (4). However, more than 10 years after the conclusion of these studies there is little to no mechanistic explanation for how aging contributes to a change in estrogen signaling.One possibility is that there are age-related changes in the way the brain responds to estrogens. We hypothesized that there are intrinsic changes in the function of estrogen receptors in the brain with advanced age, and estrogen receptor ␤ (ER␤) 1 in particular has been shown to be a critical regulator of many neurobiological functions. An important component of ER␤ signaling is requisite associations with intracellular coregulatory proteins. ...

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“…The frequency of the GnRH pulses seems to influence the different effects on cell function of the gonadotropes [2][3][4]. Recently, we demonstrated that GnRH stimulates the expression of annexin A5 mRNA in gonadotropes [5][6][7][8]. Because ovariectomy enhanced annexin A5 expression in the gonadotropes and estradiol inhibited it, the expression of pituitary annexin A5 was thought to be physiologically regulated by hypothalamic GnRH [6].…”

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confidence: 99%

Gonadotropin Releasing Hormone (GnRH) Enhances Annexin A5 mRNA Expression through Mitogen Activated Protein Kinase (MAPK) in L.BETA.T2 Pituitary Gonadotrope Cells

et al. 2008

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Abstract. The mechanism by which GnRH stimulates annexin A5 expression was examined with LβT2 gonadotrope cells. Continuous stimulation with GnRH analog (GnRHa, Des-Gly10 [Pro9]-GnRH ethylamide) transiently elevated LHβ mRNA expression while maintaining annexin A5 mRNA at high levels for 24 h. GnRH antagonist blocked the effect of GnRHa on annexin A5. While 12-O-tetradecanoyl-phorbol-13 acetate, a protein kinase C activator, increased the expression of annexin A5 mRNA, bisindolylmaleimide, an inhibitor of protein kinase C, suppressed GnRHa-stimulated expression of annexin A5 and LHβ mRNA. GnRHa stimulation of LHβ mRNA was inhibited to a greater extent than annexin A5 by a calcium chelator BAPTA/AM. Although a calcium ionophore ionomycin stimulated the expression of both genes, only LHβ was down-regulated. The MAPK kinase inhibitor PD98059 inhibited GnRHa induction of annexin A5 but not LHβ mRNA. EGF stimulated the expression of annexin A5 mRNA but caused only a transient effect on LHβ mRNA expression. These results indicate that GnRH stimulation of signaling pathway for annexin A5 mRNA expression is distinct from that of LHβ mRNA and dependent more on MAPK. GnRH is a hypothalamic neuropeptide that regulates pituitary gonadotropin secretion. GnRH neuron secretes GnRH in a pulsatile fashon at the median eminence of the hypothalamus. Portal blood also shows pulsatile fluctuations of GnRH [1]. The frequency of the GnRH pulses seems to influence the different effects on cell function of the gonadotropes [2][3][4]. Recently, we demonstrated that GnRH stimulates the expression of annexin A5 mRNA in gonadotropes [5][6][7][8]. Because ovariectomy enhanced annexin A5 expression in the gonadotropes and estradiol inhibited it, the expression of pituitary annexin A5 was thought to be physiologically regulated by hypothalamic GnRH [6]. We also demonstrated that annexin A5 participates in GnRH control of gonadotropin secretion. Annexin A5 itself stimulates both LH and FSH release, while an annexin A5 antisense oligonucleotide reduces GnRH stimulation of LH [7]. These findings suggest that intracellular annexin A5 is requisite for GnRH stimulation of gonadotropin secretion.In mammals, the annexin family consists of a group of at least 12 Ca 2+ -dependent phospholipid binding proteins [9,10]. Annexin A1 was first identified as a mediator of the anti-inflammatory activity of glucocorticoids [11]. The identification of other annexins followed, including annexin A5 that was discovered as a protein that inhibits phospholipase A 2 and suppresses blood coagulation [12,13]. These activities are thought to be due to its ability to bind phospholipids, although it is not clear whether these activities are relevant to physiological function. However, as we showed in the gonadotropes, annexin A5 may be at least necessary for an intracellular signaling in some cell types [14][15][16].

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Ovariectomy enhances the expression and nuclear translocation of annexin 5 in rat anterior pituitary gonadotrophs

Cited by 20 publications

References 29 publications

Immunohistochemical Localization of Annexin A5 in the Mammary Gland of Rats: Up-Regulation of Expression by Pup Removal

Immunohistochemical Localization of Annexin A5 in the Mammary Gland of Rats: Up-Regulation of Expression by Pup Removal

Age-dependent Effects of 17β-estradiol on the Dynamics of Estrogen Receptor β (ERβ) Protein–Protein Interactions in the Ventral Hippocampus

Gonadotropin Releasing Hormone (GnRH) Enhances Annexin A5 mRNA Expression through Mitogen Activated Protein Kinase (MAPK) in L.BETA.T2 Pituitary Gonadotrope Cells

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