Biomedical subjects
Publications and source records attributed to D K Sarkar.
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The concentration of LH releasing factor (LH-RF) was measured by radioimmunoassay in blood collected from the cut pituitary stalk of long-term ovariectomized rats anaesthetized with Althesin. Stalk plasma LH-RF concentrations were increased immediately after ovariectomy (carried out at oestrus) and low at 2 and 4 days after operation. The concentrations then began to increase to reach a level at 24-28 days which was significantly higher than the concentrations during the oestrous cycle except for the time of the ovulatory surge at pro-oestrus. This pattern was similar to that of the concentrations of LH in jugular venous plasma taken from the same animals before exposure of the pituitary stalk. Like peripheral plasma LH concentrations, the concentrations of LH-RF in stalk plasma fluctuated and fell significantly and rapidly after the intravenous injection of 1 microgram oestradiol-17 beta. The release of LH-RF in long-term ovariectomized rats, into which had been implanted an oestradiol-containing Silastic capsule, was similar to the diurnal pattern of LH release; the afternoon increase in stalk plasma LH-RF concentration could be blocked by sodium pentobarbitone administered at 13.00 h and augmented by administering this anaesthetic at 13.00 h of the preceding day. The stalk plasma LH-RF concentrations in animals injected with oestradiol benzoate (OB) followed 72 h later with either OB or progesterone were lower than the concentrations in animals injected only with oil. These data show that in the rat (1) ovarian steroids could moderate LH release ('negative feedback') by inhibiting LH-RF release, and that in long-term ovariectomized animals (2) the oestradiol-induced circadian pattern of LH release is due to a circadian pattern of LH-RF release, and (3) the surge of LH produced by administering OB followed by either OB or progesterone is probably due mainly to a massive increase in the responsiveness of the anterior pituitary gland to LH-RF.
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The mechanism of the first (pubertal) preovulatory gonadotrophin surge was investigated in Wistar rats by measuring (1) LH releasing factor (LH-RF) in pituitary stalk plasma and in extracts of hypothalamic and preoptic tissue, (2) LH and FSH in peripheral plasma and extracts of anterior pituitary tissue and (3) the LH and FSH response to LH-RF. The mechanism of the first surge appeared broadly to resemble that in the adult. That is, the gonadotrophin surge which occurs on the afternoon of the day before vaginal opening was found to coincide with a surge of immunoreactive LH-RF in pituitary stalk plasma and a significant increase in pituitary responsiveness to LH-RF. The magnitude of the change in pituitary responsiveness was, however, less at puberty than in the adult while the peak of the LH-RF surge was higher at puberty. The surges of LH-RF in stalk plasma and gonadotrophin in peripheral plasma corresponded relatively precisely with a fall in the preoptic and hypothalamic content of LH-RF and in the pituitary content of LH and FSH, suggesting that, in contrast with the adult, the synthesis of LH-RF and gonadotrophin at puberty cannot keep up with their release. A significant increase in stalk plasma LH-RF concentration occurring concomitantly with a surge of LH could be induced on the afternoon of Day 32 of life by administering pregnant mare serum (PMS) ON Day 30 (about 10 days before vaginal opening). This, together with other evidence, suggests that the timing of the first gonadotrophin surge depends upon the capacity of the ovary to secrete oestradiol in the form of a surge. The fact that no significant increase in the pituitary responsiveness to LH-RF occurred in PMS-treated rats could account for the fact that the height of the gonadotrophin surge in these animals is only a third that of the spontaneous surge. No significant change in peripheral plasma LH or stalk plasma LH-RF concentrations was found around the time of vaginal opening or cornification in female rats given 1.25 mg testosterone propionate on Day 4 (androgenized female rats). Studies on the effect of ovariectomy and/or adrenalectomy suggested that the ovary and adrenal are involved in the timing of vaginal opening in normal but not in androgenized female animals.
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The effect of thymosin on in vitro reactivity of peripheral lymphocytes to phytohemagglutinin, concanavalin A, and the formation of spontaneous E-rosettes in 54 patients with metastatic carcinomas has been studied. Thymosin increased lymphocyte responses to PHA and Con A in only 10 patients, with predominant effect seen with Con A. Twenty patients showed depressed baseline levels of E-rosettes which were increased to normal or subnormal levels after incubation with thymosin. No distinct correlation was noted between the clinical stage of the disease and the ability of lymphocytes to form E-rosettes. Although the exact mechanism by which the thymus exerts its influence on host resistance is not clearly defined, present evidence supports the concept that the thymic hormone, thymosin, may be an important addition in treatment of cancer patients by increasing cell-mediated immunity.
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Recently it has been shown that lactotropic cells in the anterior pituitary gland produce and secrete transforming growth factor-beta 1-(TGF-beta 1) like peptide. The in vivo action(s) of this peptide growth factor on lactotropic cells have not been studied. In this study we determined the effects of TGF-beta 1 on lactotropic cell function in estradiol-17 beta-treated ovariectomized rats. Intrapituitary administration of TGF-beta 1 significantly inhibited plasma levels of prolactin (PRL). In addition, TGF-beta 1 decreased pituitary weight and the DNA synthesis in lactotropes and reduced the PRL levels in the pituitary. These results suggest that TGF-beta 1 may be a physiological regulator of PRL secretion and lactotropic cell proliferation.
Natural and synthetic estrogens have been associated with several types of human and animal cancers including prolactin-secreting pituitary tumors in Fischer 344 rats. These prolactin-secreting tumors are highly angiogenic and their growth is angiogenic dependent. In the present study we have utilized this model to evaluate the effect of 2-methoxyestradiol (2-ME), an endogenous estrogen metabolite that is a potent inhibitor of endothelial cell proliferation in vitro, on estrogen-induced pituitary tumor growth and angiogenesis. Adult female rats were implanted (subcutaneously) with a silastic capsule containing estradiol-17beta (E2). After seven days of constant E2 exposure animals were injected (sc) daily with 25 mg/kg of 2-ME and killed either three or 8 days later. Changes in pituitary weight and proliferating cell nuclear antigen (PCNA) labeling index indicated growth while degree of angiogenesis was determined immunohistochemically using factor VIII related antigen. The results indicate that 2-ME inhibited estrogen-induced lactotroph growth by 32% and tumor angiogenesis by 89%. Furthermore, vascular endothelial growth factor (VEGF) expression, evaluated by immunohistochemical analysis, was down-regulated concomitant with tumor angiogenic suppression. These studies suggest that 2-ME may have therapeutic potential for hormone-induced cancer and that its angiostatic activity may be modulated through down-regulation of VEGF expression.