No abstract

In the past 100 years, vaccination has contributed immensely to public health by preventing a number of infectious diseases. Attenuated, killed or part of the microorganism is employed to stimulate the immune system against it. Progress in biotechnology has provided protective immunity through DNA vaccines. In recent years, nanovaccine is a novel approach to the methodology of vaccination. Nanomaterials are delivered in the form of microspheres, nanobeads or micro-nanoprojections. Painless, effective and safe needle-free routes such as the intranasal or the oral route, or patches of microprojections to the skin are some of the approaches which are in the experimental stage at present but may have a great future ahead in nanovaccination.

Follicle-stimulating hormone is important for mammalian reproduction. It acts through specific receptors located on the plasma membrane of granulosa cells in ovaries and Sertoli cells in testes. The binding of follicle-stimulating hormone to its receptor activates intracytoplasmic signaling pathways leading to steroidogenesis. These steroids in turn regulate the follicle-stimulating hormone action from the anterior pituitary through exerting negative feedback effect. In addition to steroids, non-steroidal factors secreted by the ovaries are believed to modulate follicle-stimulating hormone action through autocrine/paracrine mode. One such low molecular weight peptide referred to as follicle-stimulating hormone receptor-binding inhibitor-8 purified from human follicular fluid has been extensively studied. Follicle-stimulating hormone receptor-binding inhibitor-8 has been shown to inhibit binding of follicle-stimulating hormone to its receptor. The present article describes the effect of follicle-stimulating hormone receptor-binding inhibitor-8 on follicle-stimulating hormone-induced signaling in rat granulosa cells. Follicle-stimulating hormone receptor-binding inhibitor-8 inhibited the follicle-stimulating hormone-induced cAMP, and the effect was observed to be mediated through the protein kinase A. Further, an inhibitory effect of follicle-stimulating hormone receptor-binding inhibitor-8 on the granulosa cell proliferation was evaluated using COV434 cell line which is derived from the human granulosa cell tumor. The effect of the peptide on the cell cycle analysis showed an increase in apoptotic population and the arrest of G1 phase. These findings suggest that follicle-stimulating hormone receptor-binding inhibitor-8 acts as a follicle-stimulating hormone antagonist and affects the follicle-stimulating hormone-mediated signaling and proliferation in the granulosa cells.

Follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI-8) is a novel octapeptide purified from human ovarian follicular fluid. In vitro, it inhibits the binding of FSH to granulosa cells and in vivo, it induces atresia in developing follicles in rodents. This peptide, when administered to marmosets and bonnet monkeys, altered the circulating progesterone levels. This study was carried out to elucidate structure of the FRBI-8 and understand its mechanism of inhibiting interaction of FSH to its receptors. Homology modeling predicted that the FRBI-8 adopts a turn and random coil. This is further confirmed by circular dichroism and NMR. Docking studies of the FRBI-8 with reported FSH-FSHR hormone binding (FSHR(HB)) domain complex using ZDOCK algorithm revealed that the FRBI-8 binds to FSHbetaL2-FSHR(HB) binding interface which is otherwise known to be crucial for activation of signal transduction cascade. FRBI-8 analogs were designed by replacing the acidic amino acid residues at positions 2, 5 and 6 with Ala, individually. Docking studies revealed that D6A mutant (FRBI-8(D6A)) had a higher binding affinity than the native FRBI-8. In vitro radioreceptor assay with FRBI-8(D6A) showed 50% lower IC(50) compared with the FRBI-8, confirming the in silico observations. Thus, the study reveals that both FRBI-8 and FRBI-8(D6A) interfered with the binding of FSH to its receptor.