title: Effect of single-chain ovine gonadotropins with dual activity on ovarian function in sheep.
abstract: We examined the half-life and biological activity of two single-chain proteins that combined portions of ovine FSH and LH. We proposed the hypothesis that these chimeric proteins would display LH and FSH activities and would promote follicle maturation in ewes. Estrus activity was synchronized using progestogen-impregnated vaginal pessaries. To negate the impact of endogenous LH and FSH, animals received serum-containing antibodies against GNRH 1 day before pessary removal (PR). At PR sheep (five animals per group) received a single injection (10 IU/kg, i.v.) of either the ovine-based (oFcLcα) gonadotropin analog, an ovine-based analog containing oLHβ truncated at the carboxyl terminus (oFcL(ΔT)cα), or a human-based gonadotropin analog (hFcLcα). Control animals received a comparable amount of gonadotropin-free protein. Ovulation was induced 3 days after PR using human chorionic gonadotropin (1000 IU, i.v.). Ovaries were collected 11 days after PR. Neither estradiol (E2) or progesterone (P4) production, development of preovulatory follicles or corpora lutea (CL) were noted in control animals receiving gonadotropin-free protein. Significant increase in the synthesis of E2 and P4 was noted in sheep receiving the dually active gonadotropin analogs. The number of CLs present 11 days after PR was significantly increased in sheep receiving the chimeric glycoproteins compared with control animals. The magnitude of the secretory and ovarian responses did not differ between hFcLcα and oFcLcα or between oFcLcα and oFcL(ΔT)cα. Immunoactivity of LH and FSH was low in control animals, but was significantly elevated in sheep receiving the gonadotropin analogs. In conclusion, ovine-based gonadotropin analogs are functionally active in sheep and a single injection is adequate to induce the development of multiple ovulatory follicles.
authors.affiliation: Department of Animal ScienceUniversity of California, Davis, One Shields Avenue, Davis, California 95616, USADepartments of Developmental Biology and Obstetrics and GynecologyWashington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USADepartment of AnimalDairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, Utah 84322, USADepartment of Animal ScienceUniversity of California, Davis, One Shields Avenue, Davis, California 95616, USADepartments of Developmental Biology and Obstetrics and GynecologyWashington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USADepartment of AnimalDairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, Utah 84322, USA hrutigliano@gmail.com.
authors.forename: Heloisa M
authors.initials: HM
authors.lastname: Rutigliano
authors.affiliation: Department of Animal ScienceUniversity of California, Davis, One Shields Avenue, Davis, California 95616, USADepartments of Developmental Biology and Obstetrics and GynecologyWashington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USADepartment of AnimalDairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, Utah 84322, USA.
authors.forename: Betty M
authors.initials: BM
authors.lastname: Adams
authors.affiliation: Department of Animal ScienceUniversity of California, Davis, One Shields Avenue, Davis, California 95616, USADepartments of Developmental Biology and Obstetrics and GynecologyWashington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USADepartment of AnimalDairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, Utah 84322, USA.
authors.forename: Albina
authors.initials: A
authors.lastname: Jablonka-Shariff
authors.affiliation: Department of Animal ScienceUniversity of California, Davis, One Shields Avenue, Davis, California 95616, USADepartments of Developmental Biology and Obstetrics and GynecologyWashington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USADepartment of AnimalDairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, Utah 84322, USA.
authors.forename: Irving
authors.initials: I
authors.lastname: Boime
authors.affiliation: Department of Animal ScienceUniversity of California, Davis, One Shields Avenue, Davis, California 95616, USADepartments of Developmental Biology and Obstetrics and GynecologyWashington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USADepartment of AnimalDairy and Veterinary Sciences, School of Veterinary Medicine, Utah State University, 4815 Old Main Hill, Logan, Utah 84322, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Adams
mesh_terms: D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000276:immunology; D006207:Half-Life; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007114:Immunization; D007986:Luteinizing Hormone / Q000494:pharmacology*; D010053:Ovary / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010060:Ovulation / Q000187:drug effects / Q000502:physiology*; D011374:Progesterone / Q000378:metabolism; D011863:Radioimmunoassay; D012756:Sheep
chemical_list: D006063:Chorionic Gonadotropin; D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone