Biomaterial Database

Desensitization of brain opiate receptor mechanisms by gonadal steroid treatments that stimulate luteinizing hormone secretion. 1988

L A Berglund, and H Derendorf, and J W Simpkins

Department of Pharmocodynamics, University of Florida College of Pharmacy, Gainesville 32610.

We studied the effects of two ovarian steroid treatments that induce proestrous-like surges in LH secretion on responsiveness to morphine sulfate (MS), as measured by induced hypothermic, antinociceptive, behavioral, and LH secretory changes. Ovariectomized rats received no steroids (OVX), 7.5 micrograms estradiol benzoate 2 days before the experiment (EB), or EB and then 5 mg progesterone 48 h later (EBP). MS administration coincided with the steroid-induced LH hypersecretion that occurs in the EB and EBP rats at 1530-1630 h. Serum LH concentrations were determined 30 min after administration of MS. In OVX and EB rats, MS caused a dose-dependent decrease in serum LH, but even 20 mg/kg MS did not alter serum LH during the EBP-induced LH surge. Brain-mediated morphine-induced analgesia was evaluated in the three steroid treatment groups from measurement of latency to pawlick on a hot plate. EB and EBP rats were less responsive than OVX rats to MS-induced antinociception. EB and EBP rats were also less responsive than OVX animals to the spinal cord-mediated analgesia due to MS, as calculated by tail-flick latency. MS-induced hypothermia revealed a responsiveness order of OVX greater than EB greater than EBP. Whereas MS caused a dose-dependent reduction in locomotor activity in OVX and EB rats, EBP rats showed marked hyperactivity at low MS doses and were less responsive to the suppression of locomotor activity at higher doses. These marked steroid-induced changes in MS responsiveness could not be explained by altered pharmacokinetic disposition of morphine. These data indicate that treatment with EBP, which stimulates a preovulatory-like LH surge, decreases the ability of MS to induce hypothermic, antinociceptive, and behavioral responses and abolishes its capacity to suppress LH release. These effects of gonadal steroids were not observed before the LH surge, which suggests that this surge is linked to the decline in MS sensitivity. Further, the diminished response to MS appears to be a function of the magnitude of the LH surge.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
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
D009020	Morphine	The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.	Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D009043	Motor Activity	Body movements of a human or an animal as a behavioral phenomenon.	Activities, Motor,Activity, Motor,Motor Activities
D010052	Ovariectomy	The surgical removal of one or both ovaries.	Castration, Female,Oophorectomy,Bilateral Ovariectomy,Bilateral Ovariectomies,Castrations, Female,Female Castration,Female Castrations,Oophorectomies,Ovariectomies,Ovariectomies, Bilateral,Ovariectomy, Bilateral
D010147	Pain Measurement	Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.	Analgesia Tests,Analogue Pain Scale,Formalin Test,McGill Pain Questionnaire,Nociception Tests,Pain Assessment,Pain Intensity,Pain Severity,Tourniquet Pain Test,Visual Analogue Pain Scale,Analog Pain Scale,Assessment, Pain,McGill Pain Scale,Visual Analog Pain Scale,Analgesia Test,Analog Pain Scales,Analogue Pain Scales,Formalin Tests,Intensity, Pain,Measurement, Pain,Nociception Test,Pain Assessments,Pain Intensities,Pain Measurements,Pain Questionnaire, McGill,Pain Scale, Analog,Pain Scale, Analogue,Pain Scale, McGill,Pain Severities,Pain Test, Tourniquet,Questionnaire, McGill Pain,Scale, Analog Pain,Scale, Analogue Pain,Scale, McGill Pain,Severity, Pain,Test, Analgesia,Test, Formalin,Test, Nociception,Test, Tourniquet Pain,Tests, Nociception,Tourniquet Pain Tests
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
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D011957	Receptors, Opioid	Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.	Endorphin Receptors,Enkephalin Receptors,Narcotic Receptors,Opioid Receptors,Receptors, Endorphin,Receptors, Enkephalin,Receptors, Narcotic,Receptors, Opiate,Endorphin Receptor,Enkephalin Receptor,Normorphine Receptors,Opiate Receptor,Opiate Receptors,Opioid Receptor,Receptors, Normorphine,Receptors, beta-Endorphin,beta-Endorphin Receptor,Receptor, Endorphin,Receptor, Enkephalin,Receptor, Opiate,Receptor, Opioid,Receptor, beta-Endorphin,Receptors, beta Endorphin,beta Endorphin Receptor,beta-Endorphin Receptors
D001831	Body Temperature	The measure of the level of heat of a human or animal.	Organ Temperature,Body Temperatures,Organ Temperatures,Temperature, Body,Temperature, Organ,Temperatures, Body,Temperatures, Organ