Abstract:
:Local androgen synthesis in prostate cancer (PC) may contribute to the development of castration-resistant PC (CRPC), but pathways controlling intratumoral steroidogenic enzyme expression in PC are unknown. We investigated the effects of activin, a factor involved in the regulation of PC growth and steroidogenic enzyme expression in other steroidogenic tissues, on intratumoral steroidogenesis in PC. Activin A effects and regulation of the activin-signaling pathway molecules were studied in the PC cell lines LNCaP, VCaP, and PC-3 and in 13 individual PC xenograft models. Also, expression levels of inhibin βA- and βB-subunits (INHBA and INHBB) and of the activin antagonist follistatin were quantitated in patient PC tissues. Activin A induced the expression and enzyme activity of 17β-hydroxysteroid dehydrogenase enzyme AKR1C3 in LNCaP and VCaP cells. Inhibition of endogenous activin A action in the PC-3 cell line decreased AKR1C3 levels and consequently testosterone synthesis. In return, androgens suppressed INHBA expression in both VCaP cells and the PC xenograft models. The antiproliferative effects of activin A were opposed by physiological concentrations of androstenedione in LNCaP cells. In patient PC tissues, expression levels of INHBA were increased in CRPC samples and correlated with AKR1C3 levels. Moreover, a high ratio of activin subunits to follistatin was associated with a worse metastasis-free survival in patients. In conclusion, activin A is controlled by androgens in PC models and regulates local androgen production. Activin A thus seems to mediate (residual) intratumoral androgen levels and could form a novel therapeutic target in CRPC.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Hofland J,van Weerden WM,Steenbergen J,Dits NF,Jenster G,de Jong FHdoi
10.1210/en.2011-2065subject
Has Abstractpub_date
2012-12-01 00:00:00pages
5726-34issue
12eissn
0013-7227issn
1945-7170pii
en.2011-2065journal_volume
153pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::Liver X receptors (LXRs) are nuclear receptors with established roles in cholesterol, lipid, and carbohydrate metabolism, although their function in adipocytes is not well characterized. Increased adipose tissue mass in obesity is associated with increased adipocyte lipolysis. Fatty acids (FA) generated by lipolysis c...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0676
更新日期:2009-09-01 00:00:00
abstract::Puberty is associated with an increase in the plasma concentration of sex steroids, GH, and insulin-like growth factor-I (IGF-I). Gonadal steroid hormones are important for the normal pubertal growth spurt and skeletal growth. The mechanism by which gonadal steroids induce skeletal growth is still not fully understood...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.4.6618
更新日期:1999-04-01 00:00:00
abstract::Nonsteroidal anti-inflammatory drugs (NSAIDs) play potential roles in chemoprevention of colon cancer and others by inhibiting prostaglandin synthesis. In this report, we used LNCaP cells, an androgen-responsive human prostate carcinoma cell line, to study the effects of two NSAIDs, flufenamic acid (FA) and piroxicam ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.11.7246
更新日期:1999-11-01 00:00:00
abstract::3-Iodothyronamine (T(1)AM) is an endogenous thyroid hormone derivative with unknown biosynthetic origins. Structural similarities have led to the hypothesis that T(1)AM is an extrathyroidal metabolite of T(4). This study uses an isotope-labeled T(4) [heavy-T(4) (H-T(4))] that can be distinguished from endogenous T(4) ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-1254
更新日期:2012-11-01 00:00:00
abstract::Altered leptin action has been implicated in the pathophysiology of heart failure in obesity, a hallmark of which is extracellular matrix remodeling. Here, we characterize the direct influence of leptin on matrix metalloproteinase (MMP) activity in primary adult rat cardiac fibroblasts and focus on elucidating the mol...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-1166
更新日期:2011-05-01 00:00:00
abstract::Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL leve...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2016-1444
更新日期:2017-01-01 00:00:00
abstract::Inflammatory mediators, such as cytokines and prostaglandins, play a fundamental role in estrogen-dependent breast cancer through their ability to up-regulate aromatase expression and subsequent local production of estrogens in the breast. To study the link between estrogens and inflammation further, we examined the r...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0352
更新日期:2008-12-01 00:00:00
abstract::Thyroid hormones regulate bone homeostasis, and exogenously induced hyperthyroidism and hypothyroidism in mice was recently found to be associated with an altered expression of the Wnt inhibitor Dickkopf-1 (Dkk1), a determinant of bone mass. Here, we assessed the role of Dkk1 in thyroid hormone-induced changes in bone...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2018-00998
更新日期:2019-03-01 00:00:00
abstract::The beta-isoform of protein kinase C (PKC) has paradoxically been suggested to be important for both insulin action and insulin resistance as well as for contributing to the pathogenesis of diabetic complications. Presently, we evaluated the effects of knockout of the PKCbeta gene on overall glucose homeostasis and in...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.10.7073
更新日期:1999-10-01 00:00:00
abstract::In female mammals, reproduction is sensitive to the availability of metabolic fuels, and food deprivation has been shown to suppress pulsatile LH secretion, attenuate the preovulatory LH surge, and prevent ovulation. It has been suggested that food deprivation impairs fertility by reducing the secretion of GnRH by GnR...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.5.1425420
更新日期:1992-11-01 00:00:00
abstract::Adipose tissue secretes a variety of bioactive signaling molecules, termed adipokines, which regulate numerous biological functions including appetite, energy balance, glucose homeostasis, and inflammation. Chemerin is a novel adipokine that regulates adipocyte differentiation and metabolism by binding to and activati...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1490
更新日期:2012-02-01 00:00:00
abstract::We have examined the regulation of an insulin-like growth factor-binding protein-3 (IGFBP-3) protease secreted by MCF-7 human breast cancer cells using a ligand-binding assay that relies on the decrease in affinity for des(1-3)IGF-I that occurs when IGFBP-3 becomes proteolyzed. IGFBP-3 protease activity was not altere...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.141.9.7684
更新日期:2000-09-01 00:00:00
abstract::To further our understanding of the role of pituitary gonadotropin secretion in the control of corpus luteum function during the primate menstrual cycle, we have used an experimental model which enables us to directly control pituitary gonadotropin secretion throughout the luteal phase. Specifically, we have asked whe...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-3-1043
更新日期:1985-09-01 00:00:00
abstract::Notch signaling directs cell fate during embryogenesis by influencing cell proliferation, differentiation, and apoptosis. Notch genes are expressed in the adult mouse ovary, and roles for Notch in regulating folliculogenesis are beginning to emerge from mouse genetic models. We investigated how Notch signaling might i...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-0213
更新日期:2009-02-01 00:00:00
abstract::Spontaneously hypertensive (SH) rats, extensively used as experimental models of essential human hypertension, display important alterations in the neuroendocrine reproductive axis, which manifest as markedly delayed puberty onset in females but whose basis remains largely unknown. We analyze herein in female SH rats:...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2008-1381
更新日期:2009-06-01 00:00:00
abstract::Tuberoinfundibular peptide of 39 residues (TIP39) and the PTH-2 receptor (PTH2R) constitute a peptide-receptor neuromodulator system. Based on the abundance of TIP39 fibers and axonal terminals as well as PTH2R-containing neurons and their processes in the hypothalamic para- and periventricular and arcuate nuclei TIP3...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2010-0767
更新日期:2010-12-01 00:00:00
abstract::An isolated perfused rabbit ovary preparation was used to determine the effects of cyanoketone, a potent inhibitor of 3 beta-hydroxysteroid dehydrogenase, on ovulation, ovum maturation and fertilizability, and steroid production. In the first experiment, cyanoketone (10(-4) M) was added to the perfusate of one ovary. ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-6-2555
更新日期:1987-06-01 00:00:00
abstract::Characterization of glycoconjugates synthesized by polarized immature rabbit uterine epithelial (UE) cells in vitro, their vectorial patterns of secretion, and regulation by ovarian steroid hormones are reported. Large (mol wt, greater than 230 kDa) sialomucoglycoproteins and hyaluronate were primarily (86-96%) secret...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.1.1727700
更新日期:1992-01-01 00:00:00
abstract::Three different experimental approaches were used to assess the regions on the beta-subunit of human FSH (hFSH beta) that may be altered or masked by its association with the alpha-subunit of hFSH (hFSH alpha) in the heterodimeric hFSH molecule. In a direct approach, we tested whether synthetic peptides corresponding ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-128-4-1797
更新日期:1991-04-01 00:00:00
abstract::It is well established that LH has an obligatory role in the acute production of progesterone by the primate corpus luteum in vivo because interruption of LH support to the corpus luteum at any time during the luteal phase is accompanied by an immediate and sustained fall in serum progesterone concentrations. However,...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.131.5.1425410
更新日期:1992-11-01 00:00:00
abstract::Spermatogenesis is sustained by a heterogeneous population of spermatogonia that includes the spermatogonial stem cells. However, the mechanisms underlying their establishment from gonocyte embryonic precursors and their maintenance thereafter remain largely unknown. In this study, we report that inactivation of the u...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00396
更新日期:2017-11-01 00:00:00
abstract::In this study, site-directed mutagenesis and biochemical strategies have been used to establish whether disulfide bonding between extracellular Cys residues contributes to the structural integrity of the GnRH receptor (GnRH-R) and, if so, to delineate the nature of the bonding patterns involved. The majority of G prot...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.7.5233
更新日期:1997-07-01 00:00:00
abstract::Previous studies from this laboratory have demonstrated the presence of two populations of rat Leydig cells (I and II), which differ in their capacity for hCG- or cAMP-stimulated testosterone production. In the present study, we examined the metabolism of 25-hydroxycholesterol in primary cultures of both populations o...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-117-3-1184
更新日期:1985-09-01 00:00:00
abstract::Animals maintained on retinol (vitamin A-alcohol)-deficient diets exhibit testicular atrophy and loss of the germinal epithelium. Retinoic acid (vitamin A-acid), when fed to retinol-deficient animals, does not prevent these lesions and had thus been thought not to play a role in the tests. Serum testosterone (T) level...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-6-2120
更新日期:1981-06-01 00:00:00
abstract::This study was undertaken to identify uterine insulin-like growth factor-I (IGF-I) receptors and examine the regulation of these receptors throughout the estrous cycle and after 17 beta-estradiol (E2) administration to immature rats. We have demonstrated type I IGF receptors in crude uterine membranes by binding and c...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-125-2-597
更新日期:1989-08-01 00:00:00
abstract::The mechanisms whereby tissue sensitivity to PRL is controlled are not well understood. Here we report that expression of mRNA and protein for members of the SOCS/CIS/JAB family of cytokine signaling inhibitors is increased by PRL administration in ovary and adrenal gland of the lactating rat deprived of circulating P...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.11.8466
更新日期:2001-11-01 00:00:00
abstract::Thyromimetics represent a class of experimental drugs that can stimulate tissue-selective thyroid hormone action. As such, thyromimetics should have effects on the hypothalamic-pituitary-thyroid (HPT) axis, but details of this action and the subsequent effects on systemic thyroid hormone levels have not been reported ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2018-00065
更新日期:2018-07-01 00:00:00
abstract::The conceptus and endometrium secrete large amounts of prostaglandin E₂ (PGE₂) into the porcine uterine lumen during the periimplantation period. We hypothesized that PGE₂ acts on conceptus/trophoblast cells through auto- and paracrine mechanisms. Real-time RT-PCR analysis revealed that PGE₂ receptor (PTGER)2 mRNA was...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2012-2271
更新日期:2013-10-01 00:00:00
abstract::Regulation of the lactogen specific binding sites of rat liver was studied in several different high lactogen states. The specific binding of [125I]iodo-hGH was determined as a measure of these sites. Hypophysectomy of pregnant rats produced a much smaller decrease in hepatic binding of [125I]iodo-hGH than was seen in...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-5-1168
更新日期:1976-11-01 00:00:00
abstract::The present study was undertaken to investigate the effect of the Hyp mutation and diet-induced hyperparathyroidism on renal responsiveness to PTH and forskolin and to determine whether the renal brush border membrane phosphate transport defect is expressed in the vitamin D- and calcium-deficient Hyp mouse. Our result...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-118-3-1047
更新日期:1986-03-01 00:00:00