Abstract:
:The glycoprotein FSH, a product of pituitary gonadotrope cells, regulates ovarian follicle development in females and spermatogenesis in males. FSH is a heterodimer of the common α gonadotropin subunit and the hormone-specific FSHβ subunit (a product of the Fshb gene). Using a conditional knockout approach (Cre-lox), we previously demonstrated that Fshb expression in mice depends on the transcription factors forkhead box L2 (FOXL2) and SMAD4. Deletion of Foxl2 or Smad4 alone led to FSH deficiency, female subfertility, and oligozoospermia in males. Simultaneous deletion of the two genes yielded a greater suppression of FSH and female sterility. The Cre-driver used previously was first active during embryonic development. Therefore, it is unclear whether FOXL2 and SMAD4 play important roles in the development or adult function of gonadotropes, or both. To address this question, we developed a tamoxifen-inducible Cre-driver line, which enabled Foxl2 and Smad4 gene deletions in gonadotropes of adult mice. After tamoxifen treatment, females with previously demonstrated fertility exhibited profound reductions in FSH levels, arrested ovarian follicle development, and sterility. FSH levels were comparably reduced in males 1 or 2 months after treatment; however, spermatogenesis was unaffected. These data indicate that (1) FOXL2 and SMAD4 are necessary to maintain FSH synthesis in gonadotrope cells of adult mice, (2) FSH is essential for female reproduction but appears to be unnecessary for the maintenance of spermatogenesis in adult male mice, and (3) the inducible Cre-driver line developed here provides a powerful tool to interrogate gene function in gonadotrope cells of adult mice.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Li Y,Schang G,Wang Y,Zhou X,Levasseur A,Boyer A,Deng CX,Treier M,Boehm U,Boerboom D,Bernard DJdoi
10.1210/en.2018-00100subject
Has Abstractpub_date
2018-07-01 00:00:00pages
2641-2655issue
7eissn
0013-7227issn
1945-7170pii
5001725journal_volume
159pub_type
杂志文章相关文献
ENDOCRINOLOGY文献大全abstract::For insight into transcriptional mechanisms mediating physiological responses to GH, data mining was performed on a profile of GH-regulated genes induced or inhibited at different times in highly responsive 3T3-F442A adipocytes. Gene set enrichment analysis indicated that GH-regulated genes are enriched in pathways in...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2009-0212
更新日期:2009-08-01 00:00:00
abstract::In the present study we have used a high affinity photoaffinity label (PAL) agonist (pGlu-His-Trp-Ser-125I-iodoTyr-D-Lys(para-N3-Benzoyl)-Leu-Arg-P roNHEt) and a PAL antagonist (NAcD2Nal-D4ClPhe-D3Pal-Ser-125I-iodo-NMeTyr-D-L ys(para-N3-Benzoyl)Leu-Lys(Isp) - Pro-D-Ala-NH2) to covalently label the GnRH receptor. Rat p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.133.2.8393780
更新日期:1993-08-01 00:00:00
abstract::We investigated the role of peritubular cell-Sertoli cell interactions in the control of Sertoli cell function by androgens. Decreased FSH-inducible aromatase activity and increased secretion of androgen-binding protein (ABP) were used as parameters of androgen action on Sertoli cells. It is demonstrated that cocultur...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-123-4-2100
更新日期:1988-10-01 00:00:00
abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a newly discovered neuropeptide that is present in high amounts in hypothalamic neuroendocrine neurons and potently stimulates the accumulation of cAMP within cells of the anterior pituitary. We have employed several specific antisera recognizing different ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.9.7649120
更新日期:1995-09-01 00:00:00
abstract::Active immunization against GRF at 6 months of age delays puberty in beef heifers. The objectives of the present study were to determine whether active immunization against GRF at an earlier age would affect normal onset of puberty and follicular growth and to determine whether these changes were related to alteration...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.137.5.8612500
更新日期:1996-05-01 00:00:00
abstract::Organ weight was compared in adult mice with deletion of one (IRS-1-/+) or both (IRS-1-/-) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1+/+ littermates. IRS-1-/+ mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1-/- mice showed major reductions ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.12.7219
更新日期:1999-12-01 00:00:00
abstract::Spinal cord hemisection between T2 and T3 inhibits compensatory adrenal growth when the contralateral but not the ipsilateral adrenal is removed (p less than 0.01). Pretreatment of left adrenals with 1 or 2% lidocaine, but not with saline, before removal inhibits compensatory right adrenal growth that is normally obse...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-99-6-1659
更新日期:1976-12-01 00:00:00
abstract::Several laboratories have reported the presence of an intracellular, high affinity [dissociation constant (Kd), 1-2 nM] antiestrogen-specific binding site in estrogen target tissues. In this report, we describe the binding properties and characteristics of an additional triphenylethylene antiestrogen-binding site in t...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-112-5-1823
更新日期:1983-05-01 00:00:00
abstract::SH2-containing inositol 5'-phosphatase 2 (SHIP2) is a 5'-lipid phosphatase hydrolyzing the phosphatidylinositol (PI) 3-kinase product PI(3,4,5)P(3) to PI(3,4)P(2) in the regulation of insulin signaling, and is shown to be increased in peripheral tissues of diabetic C57BL/KSJ-db/db mice. To clarify the impact of SHIP2 ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2007-0820
更新日期:2008-02-01 00:00:00
abstract::Pineal denervation by superior cervical ganglionectomy (Gx) decreased high affinity binding of estradiol (E2) to the pineal cytosol of female rats and of testosterone to the cytosol of male rats by 40 and 26% and by 75 and 80%, 5 and 14 days after sugery; hormone binding remained unchanged up to 24 h after surgery. Bi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-98-4-849
更新日期:1976-04-01 00:00:00
abstract::Impairments in the estradiol (E2)-induced surge of LH occur as aging female rodents lose reproductive cycles. These and other impairments can be substantially attenuated by ovariectomy of the young adult. In female rats, plasma PRL tends to increase with age, whereas in male rats, GH tends to decrease; PRL is regulate...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-116-2-813
更新日期:1985-02-01 00:00:00
abstract::Addition of somatostatin-14 (SRIF) inhibits corticotropin releasing factor (CRF) and forskolin-stimulated cyclic AMP formation and ACTH release from tumor cells of the mouse anterior pituitary (AtT-20/D16-16). After long-term pretreatment of these cells with SRIF, the ability of SRIF to inhibit CRF and forskolin-stimu...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-113-2-811
更新日期:1983-08-01 00:00:00
abstract::Human decidual cells synthesize and release decidual PRL (dPRL) immunologically and biochemically identical to human pituitary PRL. However, stimulators and inhibitors of PRL secretion such as TRH, bromocriptine or dopamine have no effect on dPRL release. The evidence for the involvement of Ca2+ in dPRL release is bas...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.130.6.1597150
更新日期:1992-06-01 00:00:00
abstract::Since specific binding to receptors and biological effects of insulin and insulin-like growth factors (IGFs) are demonstrable soon after the neural tube closes and organogenesis begins in the chick embryo, in the present study we have analyzed the structural characteristics and specificity of the receptors for insulin...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-121-4-1468
更新日期:1987-10-01 00:00:00
abstract::In cultured rat pituitary cells, increases in the cytosolic calcium concentration ([Ca2+]i) and LH release are induced by activation of GnRH receptors as well as by nonreceptor-mediated stimuli. Treatment of pituitary cells with the myosin light chain kinase (MLCK) inhibitor, wortmannin, attenuated GnRH-induced LH rel...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.138.4.5078
更新日期:1997-04-01 00:00:00
abstract::We describe an in vitro system for evaluating the direct effects of catecholamines on the activity of the type II iodothyronine 5'-deiodinase in dispersed rat brown adipocytes. Incubation with norepinephrine or phenylephrine for 3-4 h causes up to a 5-fold increase in deiodinase activity in these cells. As found in vi...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-120-3-1069
更新日期:1987-03-01 00:00:00
abstract::The importance of thyroid hormone (TH) in wound healing is not well understood. To gain insight, we evaluated the impact of TH deficiency on wound-healing genes in cultured keratinocytes. By RT-PCR, keratin 6a (K6a) and 16 (K16) gene expression in TH replete cells was 3.8- (P < 0.005) and 1.9-fold (P < 0.05) greater, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2003-1696
更新日期:2004-05-01 00:00:00
abstract::PRL gene expression in the anterior pituitary has been the focus of intensive investigation for many years, but very little information is available on the actual dynamics by which this process occurs in individual mammotrope cells. Here, we used single cell bioluminescent imaging microscopy and a recently refined rep...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.143.3.8682
更新日期:2002-03-01 00:00:00
abstract::Multiple interferon (IFN)-tau genes exist in cattle, but it has remained unclear how many are expressed, the extent of their variation, and whether different genes exhibit similar patterns of expression and code for proteins with similar biological activities. A total of 118 complementary DNA (cDNA) were bi-directiona...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.142.7.8249
更新日期:2001-07-01 00:00:00
abstract::Chronically elevated fatty acids contribute to insulin resistance through poorly defined mechanisms. Endoplasmic reticulum (ER) stress and the subsequent unfolded protein response (UPR) have been implicated in lipid-induced insulin resistance. However, the UPR is also a fundamental mechanism required for cell adaptati...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2011-1881
更新日期:2012-05-01 00:00:00
abstract::To examine the relationship between the expression of insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) and cell growth in a cell type with a defined IGF/IGFBP system, an ovine IGFBP-2 complementary DNA was overexpressed in C6 glioma cells. C6 cells produce IGFBP-3, IGFBP-4, a negligible amount of IGFBP-2, ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.2.6498
更新日期:1999-02-01 00:00:00
abstract::Interaction between Sertoli cells and germ cells is likely to be critical for normal development of the testis. We have established and characterized cocultures of neonatal Sertoli cells and gonocytes and have begun to study the physical and functional relationship between these cells in vitro. Cells were isolated fro...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-127-6-2812
更新日期:1990-12-01 00:00:00
abstract::The peroxisome proliferator-activated receptor-gamma (PPARgamma) transcription factor plays a pivotal role in adipocyte differentiation and metabolic regulation. The transcriptional activity of PPARgamma is positively modulated by ligand binding and negatively regulated by phosphorylation mediated by the MEK/ERK signa...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.140.1.6457
更新日期:1999-01-01 00:00:00
abstract::Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of GnRH neurosecretion. This work aims at studying disruption of that neuroendocrine event in females after early exposure to a very low dose of bisphenol A (BPA), a ubiquitous endocrine disrupting chemical. Female rats were exposed to v...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2015-1937
更新日期:2016-05-01 00:00:00
abstract::We previously reported that dexamethasone (DEX) induces dose-dependent biphasic effects on steady state somatostatin (SS) messenger RNA (mRNA) levels in normal rat islet and islet SS-producing tumor cells (1027B2), characterized by stimulation at low doses and marked inhibition at high doses. The stimulatory effect is...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo.136.6.7750460
更新日期:1995-06-01 00:00:00
abstract::Synthetic glucocorticoids (GCs), including dexamethasone (DEX), are powerful anti-inflammatory drugs. Long-term use of GCs, however, can result in metabolic side effects such as hyperglycemia, hepatosteatosis, and insulin resistance. The GC receptor (GR) and liver X receptors (LXRα and LXRβ) regulate overlapping genes...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2017-00094
更新日期:2017-04-01 00:00:00
abstract::Certain metabolic properties of hormonally responsive osteogenic sarcoma cells derived from a transplantable rat tumor have been compared with those of related normal rat bone cells. All studies were carried out on cells grown in monolayer culture. Normal rat bone cells derived by repeated collagenase/trypsin digestio...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-108-1-213
更新日期:1981-01-01 00:00:00
abstract::A time-course study was performed to correlate serum gonadotropin changes after ovariectomy (OVX) or OVX plus acute estradiol (E2) treatment with LHRH content and norepinephrine (NE) and dopamine (DA) content and turnover in the suprachiasmatic-medial preoptic region (SCH-PO), the medial basal hypothalamus (MBH), and ...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/endo-107-4-892
更新日期:1980-10-01 00:00:00
abstract::Mammalian ovaries contain sympathetic neurons expressing the low affinity neurotropin receptor (p75NTR). To date neither the role these neurons might play in ovarian physiology nor their embryological origin is known. Immunohistochemistry was used to detect postnatal changes in distribution and number of both p75NTR-p...
journal_title:Endocrinology
pub_type: 杂志文章
doi:10.1210/en.2006-0394
更新日期:2006-08-01 00:00:00
abstract::For 3 yr, 1-yr synchronized circannual rhythms were found for the chick oviduct weights, amounts of soluble protein, concentrations of the progesterone receptor in this organ, and capacity of this steroid-receptor complex in cytosol in bind in vitro to deoxyribonucleoprotein acceptor sites. By fitting the data with 1-...
journal_title:Endocrinology
pub_type: 历史文章,杂志文章
doi:10.1210/endo-107-4-1234
更新日期:1980-10-01 00:00:00