FSH receptors

Fig. 4. FSH receptor-binding potencies of equine FSH ( ), eCG purified from pregnant mate s semm (O), and endometrial cups (A). Receptor-binding in ceU membrane fractions, B/Bq from (a) horse, (b) calf, and (c) rodent testes (40). Courtesy of Butterworth-Heinemaim.

Simoni, M., Nieschlag, E., and GromoU, J. (2002) Isoforms and single nucleotide polymorphisms of the FSH receptor gene implications for human reproduction. Hum. Reprod. Update. 8,413-421. 

Follitropin alfa Activates FSH receptors Mimics effects of endogenous FSH Controlled ovulation hyperstimulation in women infertility due to hypogonadism in men SC injection 3-7 x/wk Toxicity Ovarian hyperstimulation syndrome and multiple pregnancies in women gynecomastia in men headache, depression, edema in both sexes... 

Figure 2 depicts the current concept of the mode of action of FSH on granulosa or Sertoli cells. The protein domain of the FSH molecule binds to specific FSH receptors in plasma membrane, while the carbohydrate moieties of FSH are believed to interact with membrane components either within or adjacent to the receptor molecule. Isolation and characterization of the FSH receptors will contribute to elucidating the binding site and the role of the carbohydrate moieties in the transduction of the hormonal signal. The binding of FSH to the receptors is followed by the activation of adenyl cyclase resulting in the accumulation of cAMP. 

For the use in safety pharmacology, selection of a specific method for determination of the FSH receptor concentration is not important, however biological validation of the method is very important. In reference experiments, the effect of a preceding treatment on the concentration of FSH receptors should be detected, e.g. reduction in receptor concentration after inhibition of gonadotropin secretion. 

Another rare cause of amenorrhea is the so-called resistant ovary syndrome. This primary hypogonadal condition is associated with increased concentrations of plasma FSH and LH, and ovaries that contain predominantly primordial follicles. It is thought to arise from a defect in FSH receptors. This disorder can be diagnosed only by examination of an ovarian biopsy specimen, which will exhibit functioning ovarian follicles despite the presence of amenorrhea. Ovulation can sometimes be induced in these patients with administration of high doses of gonadotropins. 

Arey, B.J., Stevis, P.E., Deecher, D.C., Shen, E.S., Frail, D.E., Negro-Vilar, A., Lopez, F.J., 1997. Induction of promiscuous G protein coupling of the follicle-stimulating hormone (FSH) receptor a novel mechanism for transducing pleiotropic actions of FSH isoforms. Mol. Endocrinol. 11,517-526. 

The actions of LH and hCG are mediated by the LH receptor, while those of FSH are mediated by the FSH receptor. These receptors couple to G, to activate the adenylyl cyclase-cyclic AMP pathway and most, if not aU, of the actions of the gonadotropins can be mimicked by cyclic AMP analogs. 

One mechanism of toxicity proposed for all phthalate esters that cause testicular toxicity involves interference with the interaction of follicle stimulating hormone (FSH) with the FSH receptor on Sertoli cells (NTP 2000). This mechanism may be applicable to di- -butyl phthalate, but no studies regarding this mechanism and di- -butyl phthalate were located. 

Several studies have been done on the biological activity of 4-TZDs. Their bioactivity includes their anticonvulsarrt, hypnotic, antitubercular, anthelmintic, cardiovascular, arrticancer, antibacterial, arttifungal, antihistaminic, antiviral, antiinflammatory, arrd follicle-stimulating hormone (FSH) receptor agonist activities. Table 9.1 irrdicates a niunber of importarrt bioactive compounds in this area [7]. 

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