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Regulation of Blood Flow to the Rabbit Corpus Luteum.

Milo Charles Wiltbank

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Abstract

This dissertation is a comprehensive investigation of the physiological and anatomical basis for the regulation of blood flow in the corpus luteum, leading to a unifying working hypothesis for the regulation of intraovarian blood flow. Reference sample withdrawal, using radioactive microspheres, was the method for measurement of blood flow. The hypothesis was tested that progesterone is a local vasodilator within the corpus luteum. Experimentally-induced decreases in progesterone synthesis--as indicated by a 60 to 80 percent reduction in serum progesterone concentration--either by the infusion of aminoglutethimide or by withdrawal of the luteotropic hormone, 17$\\beta$-estradiol, did not alter luteal vascular resistance or luteal blood flow. These results indicate that the high luteal blood flow is not acutely dependent on the high rates of progesterone synthesis. A second hypothesis was that luteotropic hormones act, at least in part, by stimulation of luteal blood flow. However, blood flow in the corpus luteum did not change following the administration of estradiol, which caused increases in uterine, vaginal and ovarian stromal blood flow, or following the administration of human chorionic gonadotropin (hCG), which caused a dramatic increase in ovarian stromal blood flow and in serum progesterone. Thus, the acute luteotropic and steroidogenic effects of estradiol and hCG are not mediated by a change in blood flow. The analysis of data revealed a significant positive correlation (r = 0.80; P $<$ 0.001) between rate of luteal blood flow and mean arterial pressure. By experimentally altering blood pressure, we observed corresponding alterations in luteal blood flow. In contrast, vascular resistance in the overian stroma changed in a direction which kept blood flow relatively constant. These experiments indicate that the luteal vasculature, in contrast to the stromal vasculature, does not autoregulate its blood flow. The structural basis for the passive behavior of luteal blood vessels was investigated. Using light and electron microscopy and immunocytochemical localization of vascular smooth muscle, the vascular bed of the corpus luteum of pseudopregnancy consisted of sinusoidal capillaries without vascular smooth muscle. These studies suggest a unique model for intraovarian blood flow regulation, wherein vascular resistance within the corpus luteum of pseudopregnancy is not acutely regulated; instead, the regulation of luteal blood flow is mediated through resistance vessels on the periphery or outside of the corpus luteum.

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This dissertation is a comprehensive investigation of the physiological and anatomical basis for the regulation of blood flow in the corpus luteum, leading to a unifying working hypothesis for the regulation of intraovarian blood flow. Reference sample withdrawal, using radioactive microspheres, was the method for measurement of blood flow. The hypothesis was tested that progesterone is a local vasodilator within the corpus luteum. Experimentally-induced decreases in progesterone synthesis--as indicated by a 60 to 80 percent reduction in serum progesterone concentration--either by the infusion of aminoglutethimide or by withdrawal of the luteotropic hormone, 17$\\beta$-estradiol, did not alter luteal vascular resistance or luteal blood flow. These results indicate that the high luteal blood flow is not acutely dependent on the high rates of progesterone synthesis. A second hypothesis was that luteotropic hormones act, at least in part, by stimulation of luteal blood flow. However, blood flow in the corpus luteum did not change following the administration of estradiol, which caused increases in uterine, vaginal and ovarian stromal blood flow, or following the administration of human chorionic gonadotropin (hCG), which caused a dramatic increase in ovarian stromal blood flow and in serum progesterone. Thus, the acute luteotropic and steroidogenic effects of estradiol and hCG are not mediated by a change in blood flow. The analysis of data revealed a significant positive correlation (r = 0.80; P $<$ 0.001) between rate of luteal blood flow and mean arterial pressure. By experimentally altering blood pressure, we observed corresponding alterations in luteal blood flow. In contrast, vascular resistance in the overian stroma changed in a direction which kept blood flow relatively constant. These experiments indicate that the luteal vasculature, in contrast to the stromal vasculature, does not autoregulate its blood flow. The structural basis for the passive behavior of luteal blood vessels was investigated. Using light and electron microscopy and immunocytochemical localization of vascular smooth muscle, the vascular bed of the corpus luteum of pseudopregnancy consisted of sinusoidal capillaries without vascular smooth muscle. These studies suggest a unique model for intraovarian blood flow regulation, wherein vascular resistance within the corpus luteum of pseudopregnancy is not acutely regulated; instead, the regulation of luteal blood flow is mediated through resistance vessels on the periphery or outside of the corpus luteum.

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Available abstract

This dissertation is a comprehensive investigation of the physiological and anatomical basis for the regulation of blood flow in the corpus luteum, leading to a unifying working hypothesis for the regulation of intraovarian blood flow. Reference sample withdrawal, using radioactive microspheres, was the method for measurement of blood flow. The hypothesis was tested that progesterone is a local vasodilator within the corpus luteum. Experimentally-induced decreases in progesterone synthesis--as indicated by a 60 to 80 percent reduction in serum progesterone concentration--either by the infusion of aminoglutethimide or by withdrawal of the luteotropic hormone, 17$\\beta$-estradiol, did not alter luteal vascular resistance or luteal blood flow. These results indicate that the high luteal blood flow is not acutely dependent on the high rates of progesterone synthesis. A second hypothesis was that luteotropic hormones act, at least in part, by stimulation of luteal blood flow. However, blood flow in the corpus luteum did not change following the administration of estradiol, which caused increases in uterine, vaginal and ovarian stromal blood flow, or following the administration of human chorionic gonadotropin (hCG), which caused a dramatic increase in ovarian stromal blood flow and in serum progesterone. Thus, the acute luteotropic and steroidogenic effects of estradiol and hCG are not mediated by a change in blood flow. The analysis of data revealed a significant positive correlation (r = 0.80; P $<$ 0.001) between rate of luteal blood flow and mean arterial pressure. By experimentally altering blood pressure, we observed corresponding alterations in luteal blood flow. In contrast, vascular resistance in the overian stroma changed in a direction which kept blood flow relatively constant. These experiments indicate that the luteal vasculature, in contrast to the stromal vasculature, does not autoregulate its blood flow. The structural basis for the passive behavior of luteal blood vessels was investigated. Using light and electron microscopy and immunocytochemical localization of vascular smooth muscle, the vascular bed of the corpus luteum of pseudopregnancy consisted of sinusoidal capillaries without vascular smooth muscle. These studies suggest a unique model for intraovarian blood flow regulation, wherein vascular resistance within the corpus luteum of pseudopregnancy is not acutely regulated; instead, the regulation of luteal blood flow is mediated through resistance vessels on the periphery or outside of the corpus luteum.

Key concepts: Corpus luteum, Rabbit (cipher), Biology, Blood flow, Mathematics, Internal medicine, Endocrinology, Medicine

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