published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

No description available.

Both estradiol and progeterone are proposed autocrine or paracrine regulators of ovarian function in primate species. However, specific receptors for these steroids have not been localized to individual compartments of the primate ovary. Using immunocytochemical techniques, estradiol receptors were detected in the germinal epithelium, but not other structures, of ovaries obtained from rhesus or cynomolgus monkeys during the follicular and luteal phases of the menstrual cycle. In contrast, progesterone receptors were present in stromal and interstitial tissue, the thecal layers of healthy and atretic follicles, as well as the functional corpus luteum. These results are consistent with the concept of a receptor-mediated role for progesterone, but not estrogen, within the predominant gametogenic and endocrine structures, e.g., the follicle and corpus luteum, of the primate ovary. The recent discovery of distinct cell types in the corpus luteum of domestic ungulates has revised concepts on the control of luteal function in these species. Studies were designed to test the hypothesis that the primate corpus luteum consists of cell subpopulations that differ in physical characteristics, function and regulation. Cells enzymatically-dispersed from the monkey corpus luteum at mid-luteal phase of the menstrual cycle differed in size (diameter) and the presence of the steroidogenic enzyme, 3β-hydroxysteroid dehydrogenase (3β-HSD). Analysis of dispersed cells for forward and 90° light scatter properties by flow cytometry revealed two distinct continua (Cα and Cβ). These continua were isolated using the sorting capabilities of the flow cytometer. Cα contained single cells of ≤ 15 μm and cell clusters; the cells were typically 3β-HSD-negative nonsteroidogenic. Cβ consisted of single cells that increased in size up to 40 μm and were 3β-HSD-positive. Cβ was divided into two regions (R₁ and R₃) and the cells isolated. R₁ cells were ≤ 15 μm whereas R₃ cells were ≥ 20 μm. Basal progesterone and estrogen production by R₃ cells was greater than that produced by R₁ cells (as determined by radioimmunoassay of the incubation media). Relative stimulation of progesterone production by hCG, cAMP or PGE₂ was not different between R₁ and R₃ luteal cells. These results support the hypothesis that the primate corpus luteum consists of distinct cell subpopulations which differ in size and steroidogenic capacity. However, the cell types which secrete progesterone are typically responsive to gonadotropin and PGE₂, possibly via a cAMP-mediated pathway.

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Opioids produce myriad effects, perhaps the most clinically relevant of which is the relief of pain. The understanding of the functions mediated by opioid systems is complicated greatly by the presence of several opioid receptor types. Understanding the functions associated with specific opioid receptors may lead to the development of receptor selective drugs which elicit only desirable effects. This dissertation addresses the possibility that supraspinal and spinal opioid δ receptors mediate and/or modulate thermal antinociceptive processes in the mouse. A number of approaches were utilized in parallel in this investigation which included: (1) the determination of the naloxone pA₂ in vivo against the opioid agonists morphine (μ), (D-Ala², NMePhe⁴, Gly-ol]enkephalin (DAMGO)(μ) and [D-Pen², D-Pen⁵]enkephalin (DPDPE)(δ); (2) the investigation of possible cross-tolerance between morphine and DPDPE; and (3) antagonism studies using N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-Oh, (ICI 174,864)(δ), β-funaltrexamine(β-FNA)(μ) and naloxonazine (μ₁). No differences were found in the apparent pA₂ values for naloxone against morphine, DAMGO and DPDPE at either supraspinal or spinal sites, but was demonstrated in the spinal cord. The antinociceptive effects of i.c.v. morphine and DAMGO were antagonized by β-FNA and naloxonazine, but not ICI 174,864. I.c.v. DPDPE antinociception was blocked by ICI 174,864, but not β-FNA or naloxonazine. Neither ICI 174,864 nor naloxonazine blocked the antinociceptive effects of i.th. morphine or DAMGO. ICI 174,864, but not naloxonazine, antagonized i.th. DPDPE antinociception. I.th. morphine, but not i.th. DPDPE antinociception was blocked by β-FNA. Co-administration of sub-effective doses of DPDPE and DAMA were shown to potentiate and attenuate, respectively, i.c.v., morphine antinociception. This potentiation was evident in naive and morphine tolerant mice, and was blocked by ICI 174,864. The modulatory effects of DPDPE and DAMA were blocked by β-FNA, but not naloxonazine. In contrast the supraspinal sites, i.th. DPDPE had no effect upon i.th. morphine antinociception. Collectively, the data demonstrate that supraspinal and spinal opioid δ receptors can directly mediate antinociception in the mouse. Additionally, supraspinal, but not spinal, δ receptors are also capable of indirectly modulating antinociceptive.

No description available.

No description available.

No description available.

Graduation date: 1996

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences