Disease relevance of FSH

• The binding of FSH and hCG to ovarian tumor biopsies from 31 women was analyzed to determine whether ovarian cancers contain receptors for gonadotropic hormones [1].
• Since pFF-induced luteal dysfunction was strikingly similar to spontaneous luteal phase defects found in monkeys and women, this primate model permits study of the mechanism(s) whereby FSH deficiency during recruitment and selection of the dominant follicle portends defective luteal function and infertility in women [2].
• The effect of FSH was not blocked by pretreatment with pertussis toxin [3].
• Hence, decreases in ovarian functions during the states of hypo- or hyperthyroidism may account for diminished responsiveness of the granulosa cells to FSH [4].
• The current studies demonstrate for the first time that forkhead homolog in rhabdomyosarcoma (FKHR) (FoxO1a) is expressed in porcine granulosa cells, and FSH stimulates FKHR phosphorylation and regulates its subcellular localization in this system [5].

Psychiatry related information on FSH

• This refractoriness can be reversed simply by removing FSH from the perifusion medium for a critical period of time, i.e. 2-3 h [6].

High impact information on FSH

• During the differentiation of ovarian granulosa cells, follicle-stimulating hormone (follitropin; FSH) mediates the induction of cell surface receptors for luteinizing hormone (lutropin; LH) [7].
• Thus, the induction of LH receptors by FSH does not appear to require the accumulation of a factor in the medium, nor does it appear to be mediated via FSH-stimulated progesterone synthesis [7].
• Furthermore, 1 mM aminoglutethimide, which completely blocks FSH-stimulated progesterone biosynthesis, does not decrease the induction of LH receptors by FSH [7].
• Activin, also named FSH-releasing protein, was previously shown to induce hemoglobin accumulation in K562 cells and potentiate the proliferation and differentiation of CFU-E in human bone marrow cultures [8].
• The electrophoretic mobility of radioiodinated follitropin (FSH) alpha and beta subunits as well as the alpha beta dimer changed markedly depending on the concentration of reducing agents such as dithiothreitol [9].

Chemical compound and disease context of FSH

• These results indicate that thyroid hormones might play an important role in modulating FSH-induced aromatase activity, and that the elevated plasma estrogen levels in some cases of hyperthyroidism are not due to increased ovarian secretion [10].
• It was synthesized by a baculovirus vector-insect cell system using two cDNAs encoding the glycoprotein alpha and FSH beta subunits [11].
• FSH-induced ovarian hCG receptors and ovarian weight gain in diethylstilbestrol (DES)-treated hypophysectomized immature female rats were also suppressed by LH-RHa [12].

Biological context of FSH

• The objective of this research was to determine whether plasma concentration of FSH was genetically correlated with ovulation rate and thus was a useful trait for indirect selection [13].
• It appears, therefore, that ovulation rate can be increased following increased plasma FSH concentrations at luteolysis or in the absence of such an increase [14].
• After pFF treatment on days 1-3, FSH and E2 levels in the early follicular phase were less (P less than 0.05) than those of control cycles (n = 7) [15].
• Treatment with pFF on days 18-20 of the cycle reduced the levels of circulating FSH, but serum LH, E2, P, and the length of the luteal phase remained comparable to control cycles [15].
• Administration of charcoal-extracted porcine follicular fluid (pFF) to rhesus monkeys on days 1-3 of the menstrual cycle suppressed serum FSH, but not LH, during the early follicular phase [2].

Anatomical context of FSH

• FSH-stimulated follicular secretions enhance oocyte maturation in pigs [16].
• A minimum of three blood samples/boar were obtained at greater than 4-d intervals for determination of FSH, and testes were obtained at castration or slaughter [17].
• Using primary cultures of porcine granulosa cells, we demonstrate that both the induction and maintenance of LH receptors are critically dependent upon the continual presence of FSH [7].
• Treatment with porcine follicular fluid before the administration of exogenous LRH inhibited the release of FSH, but also affected the release of LH [18].
• In contrast, specific FSH binding to a granulosa cell-theca cell (GC-TC) tumor was directly proportional to tissue concentration, and binding was maximal in the presence of 100 ng/ml [125I]FSH [1].

Associations of FSH with chemical compounds

• Line COL gilts had greater estimated breeding values for plasma concentration of FSH at d 58 than Line C2 gilts (P < .01) [13].
• Radioiodinated FSH was affinity-cross-linked with a cleavable (nondisulfide) homobifunctional reagent to its membrane receptor on the porcine granulosa cell surface as well as to a Triton X-100-solubilized form of the receptor [19].
• Serum LH, FSH, 17 beta-estradiol (E2), and progesterone (P) were measured by RIA [15].
• The administration of steroid-free charcoal-treated porcine follicular fluid to long term castrated female rhesus monkeys lowered basal serum concentrations of FSH and had almost no effect on serum LH [18].
• GHRP-2 infusion did not modify (24-h pooled) serum LH, FSH, or TSH concentrations and minimally increased serum (pooled) daily PRL (6.8 +/- 0.83 vs. 12 +/- 1.2 microg/L; P < 0.05) and cortisol (5.3 +/- 0.59 to 7.0 +/- 0.74; P < 0.05) concentrations [20].

Physical interactions of FSH

• Thus, the ability of porcine GCs to bind EGF was changed with differentiation in vivo, while both EGF-binding capacity and mitotic responsiveness were regulated by exposure to FSH in vitro [21].
• Progesterone production and progesterone receptor (PR) immunoreactivity in cumulus cells were not detected in porcine cumulus-oocyte complexes (COC) when observations were made either just after collection from the follicles or after 28 h cultivation without LH and FSH [22].
• Similarly, the number of FSH binding sites and the FSH-induced plasminogen activator activity secretion of Sertoli cells cocultured with Leydig cells were increased [23].

Regulatory relationships of FSH

• Follistatin is a glycosylated monomeric protein originally isolated from ovarian follicular fluid based on its ability to specifically inhibit pituitary FSH release [24].
• Previous studies have demonstrated FSH stimulates StAR mRNA accumulation and gene promoter activation in granulosa cells [25].
• FSH also regulated the mitotic responsiveness to EGF [21].
• Transforming growth factor-beta (TGF beta) has been reported to enhance many FSH-stimulated functions in rat granulosa cell cultures [26].
• In addition, purified recombinant alpha-inhibin proteins were partial in vitro FSH antagonists in a bioassay in which cAMP generation from 293 cells expressing the recombinant FSH receptor is used as an index of FSH biological activity [27].

Other interactions of FSH

• Addition of the combination of FSH, LH and PRL during the period of oocyte maturation marginally improved male pronuclear formation rates (41.3 vs 55.6%; P=0.06) [16].
• We conclude that FSH stimulation of IGFBP-3 transcription is mediated by cAMP via the PKA pathway and requires the P1-3 kinase and likely the MAPK pathways [28].
• The 34-kDa form of CEBPB was decreased by the protein kinase A inhibitor H89 at 4 h (with FSH treatment), and by both protein kinase A and phosphatidylinositol 3-kinase inhibitors at 24 h of treatment [29].
• This induction was mimicked by (Bu)2cAMP as well as by FSH and hCG, and the increased PR caused by LH and (Bu)2cAMP occurred in a dose-dependent manner [30].
• Surprisingly, EGF (1-50 ng/ml) did not affect FSH stimulation of a 1423-base pair StAR gene promoter-luciferase construct in transient transfection assays in porcine granulosa cells [25].

Analytical, diagnostic and therapeutic context of FSH

• Thus, selection for increased plasma concentration of FSH seems to be a practical method for increasing ovulation rate in pig breeding programs without using laparoscopy [13].
• A woman with secondary amenorrhea had very high plasma gonadotropin concentrations (especially FSH), contrasting with normal sized ovaries and antral follicles up to 5 mm at ultrasonography [31].
• Use of serial deletion constructs and site-directed mutagenesis show that a TATA box-binding protein site is required for FSH stimulation and that a specific protein 1 (Sp1) site is required for basal transcription [28].
• Spontaneous secretion of FSH from pituitary cell cultures also varied according to species and was ranked: rabbit approximately equal to sheep > pig > rat > cow [32].
• The degly hFSH showed a 44% reduction in binding when tested in a FSH radioimmunoassay utilizing a polyclonal antibody [33].

References