Biomedical subjects

Darrell W Brann

Publications and source records attributed to Darrell W Brann.

23 records · Page 2Linked to original sources

PubMed2002

Activation of the kinin system in the ovary during ovulation: role of endogenous progesterone.

BACKGROUND: Previous work by our group and others has implicated a role for kinins in the ovulatory process. The purpose of the present study was to elucidate whether endogenous progesterone, which is an intraovarian regulator of ovulation, might be responsible for induction of the kinin system in the ovary during ovulation. The gonadotropin-primed immature rat was used as the experimental model, and the role of endogenous progesterone was explored using the antiprogestin, RU486. RESULTS: The results of the study revealed that RU486 treatment, as expected, significantly attenuated ovulation. Activity of the kinin-generating enzyme, kallikrein, was elevated in the ovary in control animals prior to ovulation with peak values observed at 4 h post hCG, only to fall to low levels at 10 h, with a recovery at 20 h post hCG. RU486 treatment had no significant effect on ovarian kallikrein activity as compared to the control group. Total ovarian kininogen levels in control animals increased significantly at 12-14 h after hCG - coinciding with initiation of ovulation. Thereafter, ovarian kininogen levels fell to low levels at 20 h, only to show a rebound from 24-38 h post-hCG. RU486 treatment had no significant effect on the rise of total ovarian kininogen levels from 12-14 h after hCG; however, from 30-40 h post hCG, RU486-treated animals had significantly higher total ovarian kininogen levels versus control animals, suggesting that endogenous progesterone may act to restrain elevations of kininogens in the post-ovulatory ovary. This robust elevation of ovarian kininogen levels by RU486 was found to be primarily due to an increase in T-kininogen, which is a potent cysteine protease inhibitor. CONCLUSIONS: Taken as a whole, these results suggest that endogenous progesterone does not regulate kallikrein activity or kininogens prior to ovulation, but may provide a restraining effect on T-kininogen levels in the post-ovulatory ovary.

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PubMed2002

Basic fibroblast growth factor induces TGF-beta release in an isoform and glioma-specific manner.

The aim of the current study was to determine whether basic fibroblast growth factor (bFGF), regulates the release of transforming growth factor-beta1 (TGF-beta1) from C6 glioma cells. The results of the study show that bFGF (2, 5 and 10 ng/ml) dose dependently induced the release of TGF-beta1 from C6 glioma cells, with the 10 ng/ml dose inducing a 2- to 3-fold increase of TGF-beta1 levels. This effect was evident as early as 6 h following treatment, with maximal levels observed at 18 h. The effect of bFGF was largely on latent TGF-beta1, and was isoform specific, as bFGF had no effect on TGF-beta2 release. The bFGF effect on TGF-beta1 was also glioma specific, as no such stimulatory effect was observed in rat cortical astrocytes.

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PubMed2002

Leptin and reproduction.

Since the cloning of leptin by Friedman's laboratory in 1994, over 3000 papers have been published on leptin, making it one of the most active research areas in all of science. Leptin appears to be a pleiotrophic hormone affecting many different tissues in the body. This review focuses on the role of leptin in reproduction. Evidence is accumulating that leptin potentially has roles in the regulation of GnRH and LH secretion, puberty, pregnancy, and lactation. Reciprocal regulation of leptin and its receptors by gonadal hormones and the implications and controversies thereof are also discussed in the review. Signaling pathways utilized by leptin are starting to become more clear, particularly JAK/STAT, MAPK, and SOCS3 have been implicated as mediators/modulators of leptin effects at the cellular level. At the hypothalamic level, there is also evidence that CART (cocaine and amphetamine-related transcript) is involved as a downstream mediator of leptin effects, especially with regards to control of GnRH secretion. While leptin clearly has many effects upon the reproductive axis, defining its precise roles is not without controversies. This review presents both pro and con findings, thereby demarking controversial areas that undoubtedly will be fertile ground for future investigation.

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PubMed2002

Protective effects of estrogen and selective estrogen receptor modulators in the brain.

Within the last few years, there has been a growing interest in the neuroprotective effects of estrogen and the possible beneficial effects of estrogen in neurodegenerative diseases such as stroke, Alzheimer disease, and Parkinson disease. Here, we review the progress in this field, with a particular focus upon estrogen-induced protection from stroke-induced ischemic damage. The important issue of whether clinically relevant selective estrogen receptor modulators (SERMs) such as tamoxifen and raloxifene and estrogen replacement therapy can exert neuroprotection is also addressed. Although the mechanism of estrogen and SERM neuroprotection is not clearly resolved, we summarize the leading possibilities, including 1) a genomic estrogen receptor-mediated pathway that involves gene transcription, 2) a nongenomic signaling pathway involving activation of cell signalers such as mitogen-activated protein kinases and/or phosphatidylinositol-3-kinase /protein kinase B, and 3) a nonreceptor antioxidant free-radical scavenging pathway that is primarily observed with pharmacological doses of estrogen. The role of other potential mediatory factors such as growth factors and the possibility of an astrocyte role in neuroprotection is also discussed.

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PubMed2002

Role of the progesterone receptor in restrained glutamic acid decarboxylase gene expression in the hypothalamus during the preovulatory luteinizing hormone surge.

Previous work by our laboratory demonstrated that activation of the progesterone receptor through exogenous administration of progesterone suppressed glutamic acid decarboxylase-67 (GAD(67)) mRNA in the hypothalamus of the estrogen-primed ovariectomized rat. Since GAD(67) is the major synthetic enzyme for the inhibitory transmitter, gamma-aminobutyric acid, the finding raised the possibility that the endogenous activation of the progesterone receptor may act to restrain GAD(67) expression during the natural preovulatory gonadotropin surge during proestrus in the rat, thereby allowing GnRH secretion and the resultant LH surge. To test this hypothesis, the progesterone receptor antagonist, RU486, was administered to regularly cycling proestrous rats and the effect on GAD(67) and GAD(65) mRNA levels in the preoptic area (POA) and medial basal hypothalamus (MBH) was examined. Serum luteinizing hormone (LH) levels were also examined in order to identify correlations between changes in POA and MBH GAD levels and production of the LH surge. GAD(67) mRNA levels in the POA were increased in the cycling rat during proestrus at 18.00 h at the peak and just preceding the termination of the LH surge. There was no change in GAD(67) mRNA levels in the MBH, and GAD(65) expression was also unchanged during proestrus in the POA and MBH. Treatment with the antiprogestin RU486 resulted in an increase in GAD(67) mRNA levels at 12.00 and 14.00 h in the POA, and in the MBH at 14.00, 16.00, and 18.00 h during proestrus, effects which preceded and correlated with the attenuated LH surge in RU486-treated rats at 18.00 h. GAD(65) mRNA levels were also elevated by RU486 at 14.00 and 16.00 h in the POA, and at 14.00 h in the MBH during proestrus. These findings suggest that the progesterone receptor plays a role in restraining GAD expression in the hypothalamus during proestrus, and that this effect may be important for the production of the GnRH and LH surge.

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