Disease relevance of Fshb

• Expression of glycoprotein hormone alpha-subunit and, less commonly, free luteinizing hormone beta (LH-beta) or follicle-stimulating hormone beta is characteristic of endocrinologically inactive adenomas, a subgroup thought to be derived predominantly from the gonadotroph line [1].
• Chromatofocusing of a human pituitary tumor extract allowed for determination of the FSH B/I ratio in different pH ranges [2].
• Similarly, in the patient with gonadal dysgenesis the FSH B/I ratio rose significantly (P less than 0.05) after 3 weeks of DES treatment and declined during the posttreatment period [2].

High impact information on Fshb

• In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1-disrupted mice lacked transcripts for three gonadotrope-specific markers (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-subunit of glycoprotein hormones [3].
• Time-course studies in adult male and female rats showed that the increase in follistatin mRNA levels after GDX is rapid, with significant increases occurring within 24 h after GDX, and parallels or precedes increases in FSH beta mRNA levels and FSH secretion [4].
• After 7 d of testosterone propionate, LH beta and alpha mRNAs declined to normal levels, whereas FSH beta mRNA increased slightly [5].
• These cells, when cotransfected with regulatory regions of the common alpha, LH beta, or FSH beta subunit gene fused to a luciferase reporter gene, respond to GnRH with an increase in luciferase activity [6].
• At each FSH beta glycosylation site, we made a second amino acid substitution to inhibit glycosylation (beta Tyr9 and beta Tyr26) and an amino acid substitution that preserved glycosylation (beta Ser9 and beta Ser26) [7].

Biological context of Fshb

• Molecular mechanisms underlying gonadotrope-specific and hormonal regulation of FSHbeta gene expression remain largely unknown [8].
• Cells were transiently transfected with the rat FSHbeta promoter fused to a luciferase reporter gene (-338rFSHbeta-Luc), and a minimal activin-responsive region was identified [9].
• A Pitx2c binding site was identified within the proximal promoter, and elimination of this region also resulted in a loss of activin-regulated FSHbeta promoter activity [9].
• Transfection of Smad3, but not the highly related Smad2, led to a ligand-independent stimulation of the FSHbeta promoter activity [9].
• Synergy between activin A and gonadotropin-releasing hormone in transcriptional activation of the rat follicle-stimulating hormone-beta gene [10].

Anatomical context of Fshb

• The activins, hormones produced in the gonads and extragonadal tissues (including the pituitary), rapidly increase FSH beta messenger RNA (mRNA) and FSH secretion [11].
• These data demonstrate that the actions of these gonadal peptides on FSH secretion may be accounted for, at least in part at the level of biosynthesis, by reductions in FSH beta mRNA levels directly at the level of the anterior pituitary gland [12].
• Physiological changes in the frequency of pulsatile GnRH release from the hypothalamus result in differential stimulation of alpha-, LHbeta-, and FSHbeta-gene expression [13].
• These results reveal that Ca/CAMK II plays a central role in the transmission of pulsatile GnRH signals from the plasma membrane to the rat alpha, LHbeta, and FSHbeta subunit genes [14].
• FSH beta, as well as LH beta, and alpha-subunit mRNA levels were examined in the pituitary glands of male rats after sex steroid replacement at various times (7, 28, or 90 days) after orchiectomy [15].

Associations of Fshb with chemical compounds

• Estradiol suppressed FSH-beta PT 3-fold and had no effect on FS or betaB mRNAs [16].
• Testosterone (T) suppresses LH-beta and increases FSH-beta [16].
• The increase in FSH-beta PT after T was androgen specific [16].
• Both T and dihydrotestosterone (DHT) increased FSH-beta PT 2-fold and decreased both FS and betaB mRNA [16].
• LH beta mRNA was suppressed by all steroid treatments (p < 0.01), FSH beta was lower in only the E2 group, and alpha-subunit was reduced in both the E2 + P4 and DHT groups (p < 0.01) [17].

Regulatory relationships of Fshb

• Evidence that pituitary adenylate cyclase activating polypeptide suppresses follicle-stimulating hormone-beta messenger ribonucleic acid levels by stimulating follistatin gene transcription [18].
• Evidence that PACAP and GnRH down-regulate follicle-stimulating hormone-beta mRNA levels by stimulating follistatin gene expression: effects on folliculostellate cells, gonadotrophs and LbetaT2 gonadotroph cells [19].
• Continuous administration of GnRH analog for 1 h enhanced the expression of both FSH beta subunit and annexin 5 mRNA [20].

Other interactions of Fshb

• We have studied the role of pituitary homeobox 1 (Ptx1), a transcription factor important for regulation of many pituitary-specific genes, in the regulation of rat FSHbeta (rFSHbeta) gene transcription [8].
• One of the actions of PACAP identified previously is to decrease FSHbeta messenger RNA (mRNA) levels [18].
• We propose that PACAP contributes to the selective regulation of FSHbeta expression during maturation in the male rat, perhaps via regulation of follistatin [21].
• Preliminary data with dual labeling also revealed the presence of GH and PRL in the same cell, but complete absence of a combination such as FSH beta + GH [22].
• Expression of the GnRH receptor in the pituitary parallels that of FSHbeta [21].

Analytical, diagnostic and therapeutic context of Fshb

• In situ hybridization revealed a developmental pattern of PACAP mRNA within the PVN that is reciprocal to that of FSHbeta [21].
• Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates alpha-subunit transcription and lengthens LH-beta mRNA transcripts, but reduces FSH-beta mRNA levels in rat pituitary cell cultures [19].
• Follistatin and FSH-beta gene expression in rat pituitary cultures were also measured by competitive quantitative RT-PCR and northern analysis, respectively [19].
• One week after castration, gonadotropin subunit PT levels were increased (alpha: 3-fold, LHbeta: 6-fold, and FSHbeta: 3-fold) in a pattern similar to subunit mRNAs [23].
• When male rats were infused through arterial cannulas for 6 h with continuous GnRH (100 nM) or recombinant follistatin (5 micrograms/h), continuous GnRH suppressed FSH beta mRNA levels to 50% of the control value, and follistatin decreased expression to 61% of the control value [24].

References