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| Status |
Public on Jun 28, 2023 |
| Title |
Activating-transcription factor 3 stimulates follicle-stimulating hormone β transcription in vitro, but is dispensable for FSH production in murine gonadotropes in vivo |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Follicle-stimulating hormone (FSH), a dimeric glycoprotein produced by pituitary gonadotrope cells, regulates spermatogenesis in males and ovarian follicle growth in females. Hypothalamic gonadotropin-releasing hormone (GnRH) stimulates FSHβ subunit gene (Fshb) transcription, though the underlying mechanisms are poorly understood. To address this gap in knowledge, we examined changes in pituitary gene expression in GnRH-deficient mice (hpg) treated with a regimen of exogenous GnRH that increases pituitary Fshb but not luteinizing hormone β (Lhb) mRNA levels. Activating transcription factor 3 (Atf3) was among the most upregulated genes. ATF3 can heterodimerize with members of the AP-1 family to regulate gene transcription. Co-expression of ATF3 with JunB stimulated murine Fshb, but not Lhb, promoter-reporter activity in homologous LβT2 cells. ATF3 also synergized with a constitutively active activin type I receptor to increase endogenous Fshb expression in these cells. Nevertheless, FSH production was intact in gonadotrope-specific Atf3 knockout mice (cKO) and control littermates. Ovarian follicle development, ovulation, and litter sizes were also equivalent between genotypes. Testis weights and sperm counts did not differ between cKO and control males. Following gonadectomy, increases in LH secretion were enhanced in cKO animals. Though FSH levels did not differ between genotypes, post-gonadectomy increases in pituitary Fshb and gonadotropin α subunit expression were more pronounced in cKO mice. These data indicate that ATF3 can selectively stimulate Fshb transcription in vitro but is not required for FSH production in vivo.
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| Overall design |
25 samples analyzed. 11 females, 14 males. 5-7 replicates per condition (sex/treatment)
*** Submitter declares access to the raw data was lost. ***
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| Contributor(s) |
Alonso CA, David CD, Toufaily C, Wang Y, Zhou X, Nudelman G, Ruf-Zamojski F, Boehm U, Sealfon SC, Bernard DJ, Nair VD |
| Citation(s) |
36951304 |
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| Submission date |
Dec 13, 2022 |
| Last update date |
Jun 28, 2023 |
| Contact name |
Stuart Sealfon |
| E-mail(s) |
stuart.sealfon@mssm.edu
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| Organization name |
Icahn School of Medicine at Mount Sinai
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| Department |
Department of Neurology
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| Lab |
Sealfon
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| Street address |
One Gustave L. Levy Place
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10029 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (25)
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| GSM6820463 |
pituitaries of hpg mice, Female, placebo, 1 |
| GSM6820464 |
pituitaries of hpg mice, Female, placebo, 2 |
| GSM6820465 |
pituitaries of hpg mice, Female, placebo, 3 |
| GSM6820466 |
pituitaries of hpg mice, Female, placebo, 4 |
| GSM6820467 |
pituitaries of hpg mice, Female, placebo, 5 |
| GSM6820468 |
pituitaries of hpg mice, Female, GnRH, 6 |
| GSM6820469 |
pituitaries of hpg mice, Female, GnRH, 7 |
| GSM6820470 |
pituitaries of hpg mice, Female, GnRH, 8 |
| GSM6820471 |
pituitaries of hpg mice, Female, GnRH, 9 |
| GSM6820472 |
pituitaries of hpg mice, Female, GnRH, 10 |
| GSM6820473 |
pituitaries of hpg mice, Female, GnRH, 11 |
| GSM6820474 |
pituitaries of hpg mice, Male, placebo, 12 |
| GSM6820475 |
pituitaries of hpg mice, Male, placebo, 13 |
| GSM6820476 |
pituitaries of hpg mice, Male, placebo, 14 |
| GSM6820477 |
pituitaries of hpg mice, Male, placebo, 15 |
| GSM6820478 |
pituitaries of hpg mice, Male, placebo, 16 |
| GSM6820479 |
pituitaries of hpg mice, Male, placebo, 17 |
| GSM6820480 |
pituitaries of hpg mice, Male, GnRH, 18 |
| GSM6820481 |
pituitaries of hpg mice, Male, GnRH, 19 |
| GSM6820482 |
pituitaries of hpg mice, Male, GnRH, 20 |
| GSM6820483 |
pituitaries of hpg mice, Male, GnRH, 21 |
| GSM6820484 |
pituitaries of hpg mice, Male, GnRH, 22 |
| GSM6820485 |
pituitaries of hpg mice, Male, GnRH, 23 |
| GSM6820486 |
pituitaries of hpg mice, Male, GnRH, 24 |
| GSM6820487 |
pituitaries of hpg mice, Male, GnRH, 25 |
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| Relations |
| BioProject |
PRJNA911595 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE220809_rld-normalized.csv.gz |
6.8 Mb |
(ftp)(http) |
CSV |
| Raw data not provided for this record |
| Processed data are available on Series record |
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