Effect of prolonged exposure to oestradiol on subsequent LH secretion in ewes. 1998

M Ozturk, and R F Smith, and H Dobson
Department of Veterinary Clinical Science and Animal Husbandry, University of Liverpool, South Wirral, UK.

Abnormal follicles can produce oestradiol continuously for up to 20 days and this inhibits the hypothalamic-pituitary axis. The present experimental series was designed to determine the minimum exposure to high or low follicular phase concentrations of oestradiol that were required to exert inhibitory effects on LH surge secretion induced by additional oestradiol administered at the end of continuous exposure to oestradiol. Experiments were also included to establish whether the inhibitory effects of prolonged oestradiol were mediated at the pituitary, and whether the failure of response to the oestradiol challenge could be corrected by exposure to normal luteal phase patterns of progesterone. Treatment of ewes between 2 and 12 days with 1, 2 or 4 oestradiol implants (3 cm) totally blocked the subsequent normal LH surge in response to an oestradiol challenge in 45 of 52 ewes pretreated with oestradiol. In the seven ewes that did have an increase in LH, the response occurred at the expected time but was greatly reduced (14 versus 40 ng ml-1), and occurred only in ewes pretreated with oestradiol implants for 2 or 4 days. We were unable to establish a robust linear time-dose relationship, i.e., when ewes were treated with lower doses of oestradiol (one or two implants) for a reduced time (2, 4 or 8 days), there was random distribution of the 7 of 32 animals that had a reduced LH surge after oestradiol challenge (with four implants or 50 micrograms injection). The present study is the first to show that exposure for only 2-4 days to continuous oestradiol at late follicular phase concentrations can disrupt LH surge release. However, in oestradiol-treated ewes, LH secretion was provoked by high or low doses (0.5 mg or 0.5 microgram) of GnRH, although it was reduced by 50%, and a GnRH self-priming effect was still evident. All of these results suggest that inhibitory effects occur at the pituitary and hypothalamus. It remains to be confirmed whether the major effect is at the pituitary by reducing GnRH receptor or LH synthesis, or at the hypothalamus via inhibition of GnRH secretion.

UI MeSH Term Description Entries
D007986 Luteinizing Hormone A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Luteinizing hormone regulates steroid production by the interstitial cells of the TESTIS and the OVARY. The preovulatory LUTEINIZING HORMONE surge in females induces OVULATION, and subsequent LUTEINIZATION of the follicle. LUTEINIZING HORMONE consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH and FSH), but the beta subunit is unique and confers its biological specificity. ICSH (Interstitial Cell Stimulating Hormone),Interstitial Cell-Stimulating Hormone,LH (Luteinizing Hormone),Lutropin,Luteoziman,Luteozyman,Hormone, Interstitial Cell-Stimulating,Hormone, Luteinizing,Interstitial Cell Stimulating Hormone
D007987 Gonadotropin-Releasing Hormone A decapeptide that stimulates the synthesis and secretion of both pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE. GnRH is produced by neurons in the septum PREOPTIC AREA of the HYPOTHALAMUS and released into the pituitary portal blood, leading to stimulation of GONADOTROPHS in the ANTERIOR PITUITARY GLAND. FSH-Releasing Hormone,GnRH,Gonadoliberin,Gonadorelin,LH-FSH Releasing Hormone,LHRH,Luliberin,Luteinizing Hormone-Releasing Hormone,Cystorelin,Dirigestran,Factrel,Gn-RH,Gonadorelin Acetate,Gonadorelin Hydrochloride,Kryptocur,LFRH,LH-RH,LH-Releasing Hormone,LHFSH Releasing Hormone,LHFSHRH,FSH Releasing Hormone,Gonadotropin Releasing Hormone,LH FSH Releasing Hormone,LH Releasing Hormone,Luteinizing Hormone Releasing Hormone,Releasing Hormone, LHFSH
D010902 Pituitary Gland A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM. Hypophysis,Hypothalamus, Infundibular,Infundibular Stalk,Infundibular Stem,Infundibulum (Hypophysis),Infundibulum, Hypophyseal,Pituitary Stalk,Hypophyseal Infundibulum,Hypophyseal Stalk,Hypophysis Cerebri,Infundibulum,Cerebri, Hypophysis,Cerebrus, Hypophysis,Gland, Pituitary,Glands, Pituitary,Hypophyseal Stalks,Hypophyses,Hypophysis Cerebrus,Infundibular Hypothalamus,Infundibular Stalks,Infundibulums,Pituitary Glands,Pituitary Stalks,Stalk, Hypophyseal,Stalk, Infundibular,Stalks, Hypophyseal,Stalks, Infundibular
D011374 Progesterone The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS. Pregnenedione,Progesterone, (13 alpha,17 alpha)-(+-)-Isomer,Progesterone, (17 alpha)-Isomer,Progesterone, (9 beta,10 alpha)-Isomer
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004343 Drug Implants Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug. Drug Implant,Drug Pellet,Pellets, Drug,Drug Pellets,Implant, Drug,Implants, Drug,Pellet, Drug
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D005260 Female Females
D005498 Follicular Phase The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION. Menstrual Cycle, Follicular Phase,Menstrual Cycle, Proliferative Phase,Menstrual Proliferative Phase,Preovulatory Phase,Phase, Follicular,Phase, Menstrual Proliferative,Phase, Preovulatory,Proliferative Phase, Menstrual

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