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Biological properties of a novel follicle-stimulating hormone/human chorionic gonadotropin chimeric gonadotropin.
- Source :
-
Endocrinology [Endocrinology] 2006 Sep; Vol. 147 (9), pp. 4205-12. Date of Electronic Publication: 2006 Jun 22. - Publication Year :
- 2006
-
Abstract
- A chimeric recombinant human gonadotropin, termed C3, demonstrates both follitropic and lutropic bioactivities. The alpha-subunit construct for C3 is comprised of the recombinant wild-type human glycoprotein hormone alpha-subunit. The beta-subunit DNA construct for C3 encodes residues 1-145 from human chorionic gonadotropin (hCG)-beta with the exceptions that FSH beta amino acid 88 (D) is substituted for hCG beta amino acid 94 (R) and FSH beta amino acids 95-108 (TVRGLGPSYCSFGE) are substituted for hCG beta amino acids 101-114 (GGPKDHPLTCDDPR). C3 is a potent FSH and LH agonist able to bind and to signal through FSH and LH receptors in vitro. In in vivo bioassays optimized to quantify each type of activity, C3 was found to have lutropin and follitropin potencies at levels similar to those of recombinant human LH and recombinant human FSH, respectively. In immature rats, C3 was sufficient to support the maturation of normal ovarian follicles. Moreover, a significant portion of follicles matured by C3 ruptured in response to an ovulatory hCG stimulus and gave rise to morphologically normal oocytes. Furthermore, a low dose of C3 promoted weight gain in the rodent uterus, suggesting it also supported preparation for implantation without histological evidence of excessive luteinization of the ovary. In summary, the biological properties of C3 indicate that its chimeric nature has resulted in a fully functional, dual-acting human gonadotropin.
- Subjects :
- Amino Acid Sequence
Animals
Chorionic Gonadotropin pharmacology
Chorionic Gonadotropin, beta Subunit, Human chemistry
Chorionic Gonadotropin, beta Subunit, Human genetics
Corpus Luteum drug effects
Corpus Luteum physiology
Female
Follicle Stimulating Hormone pharmacology
Follicle Stimulating Hormone, beta Subunit chemistry
Follicle Stimulating Hormone, beta Subunit genetics
Humans
Molecular Sequence Data
Organ Size drug effects
Ovarian Follicle drug effects
Ovarian Follicle physiology
Rats
Receptors, FSH metabolism
Receptors, LH metabolism
Recombinant Fusion Proteins chemistry
Recombinant Fusion Proteins metabolism
Sequence Alignment
Uterus anatomy & histology
Chorionic Gonadotropin genetics
Follicle Stimulating Hormone genetics
Recombinant Fusion Proteins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 147
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 16794004
- Full Text :
- https://doi.org/10.1210/en.2006-0354