1984 — 1987 |
Legan, Sandra |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Neuroendocrine Control of Gonadotropin Secretion |
0.915 |
1989 |
Legan, Sandra J. |
F33Activity Code Description: To provide opportunities for experienced scientists to make major changes in the direction of research careers, to broaden scientific background, to acquire new research capabilities, to enlarge command of an allied research field, or to take time from regular professional responsibilities for the purpose of increasing capabilities to engage in health-related research. |
Do Catecholamines Mediate Estradiol Positive Feedback? @ Northwestern University |
0.943 |
1989 — 1992 |
Legan, Sandra J. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neuroendocrine Regulation of Ovine Estrous Cycles
The long-term goal of the proposed research is to elucidate the neuro- endocrine mechanisms whereby progesterone prevents short luteal phase cycles in ewes. It has been proposed that progesterone may prevent short luteal phases by promoting folliculogenesis, by stimulating luteal function, by preventing luteolysis, or a combination of these actions. Specifically, the proposed studies will examine whether progesterone modulates some of the parameters which promote folliculogenesis, namely gonadotropin secretion, or ovarian response to gonadotropins, or both. First, we will examine whether progesterone acts solely at the ovaries. Subsequent experiments will investigate whether progesterone ensures full-length luteal phases by modulating FSH or pulsatile LH secretion. Finally, the mechanism of action of progesterone in promoting folliculogenesis within the ovary will be investigated by measuring its effect on follicular steroid production and thecal and granulosa cell binding of 125I-hCG. Techniques include: radioimmunoassays for LH, FSH, estradiol, testosterone, and progesterone; sustained delivery of hormones via osmotic minipumps or Silastic implants; blood collection; cannulation of ovarian artery; active immunization against GnRH; ovariectomy; reversible termination of cycles with GnRH agonist; in vitro incubation of granulosa cells, ad measurement of ovarian thecal and granulosa cell LH receptors. The results of these studies should: (1) provide us with new insight into the neuroendocrine mechanisms controlling estrous cycles and their initiation and termination; (2) increase our knowledge of the mechanisms controlling recovery of cyclicity following treatment with GnRH agonist; (3) increase our understanding of the neuroendocrine control of short luteal phases and the prevention of short luteal phase infertility; and (4) provide us with new information regarding the role of progesterone in promoting folliculogenesis. Finally, these findings should be applicable to the clinical situations analogous to transitions between states of acyclicity and cyclicity, such as puberty, menopause, or those occurring following treatment of precocious puberty or endometriosis with GnRH agonists, or following use of GnRH agonists as contraceptives.
|
1 |
1996 — 2000 |
Legan, Sandra J. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neural Control of Luteinizing Hormone Secretion in Aging |
1 |
2008 — 2012 |
Duncan, Marilyn J. Legan, Sandra J. |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Multiple Circadian Oscillators: Regulation of a Neuroendocrine Rhythm
[unreadable] DESCRIPTION (provided by applicant): Exciting recent studies have demonstrated autonomous circadian oscillators in many regions outside of the suprachiasmatic nucleus (SCN), the site of the mammalian master circadian pacemaker. The existence of multiple oscillators had been postulated for decades, as a basis for the desynchrony of overt circadian rhythms that occurs during shift work, jet lag and depression. These extra-SCN oscillators have been studied mainly in vitro using tissues explanted from males; thus the physiological role of these oscillators is not yet known, especially in females. We propose to investigate the regulation of circadian rhythms in clock gene expression in vivo in female neuroendocrine cells, the gonadotropin releasing hormone (GnRH) neurons, because they have an easily measured, physiologically important output, the preovulatory luteinizing hormone (LH) surge. Although the LH surge depends on the SCN, the GnRH neurons themselves express the circadian clock gene Per1. Furthermore, immortalized GnRH neurons, GT1-7 cells, exhibit circadian rhythms of clock gene expression in vitro. Disruption of these molecular circadian rhythms in GT1-7 cells alters their pattern of GnRH secretion, suggesting that molecular circadian clocks are necessary for the [unreadable] secretory function of GnRH neurons. This proposal aims to study the regulation and function of a circadian molecular oscillation in native GnRH neurons in female hamsters. The specific aims are to investigate: [unreadable] [unreadable] Aim 1) the role of circadian phase advances in control of the LH surge, Aim 2) the role of SCN GABA-A receptors in control of the LH surge, Aim 3) the role of circadian clock genes in the SCN in control of the LH surge, Aim 4) the role of vasopressin as an output signal from the SCN regulating GnRH neurons, and Aim 5) the expression of PER1 in endogenous GnRH neurons and its role in the LH surge. These studies will exploit the GnRH neurons as a model system with an essential physiological role and easily measured output, in order to elucidate the regulation and function of an extra-SCN brain oscillator in vivo. [unreadable] [unreadable] Understanding multiple oscillators is important for the amelioration of internal desynchrony of circadian rhythms that occurs during shift work and jet lag. Also, by studying females, the findings of this project may be relevant to the disruptions in circadian hormone rhythms seen in women with affective disorders.This project seeks to understand the regulation and interaction of multiple circadian oscillators that regulate circadian neuroendocrine rhythms. Understanding multiple circadian oscillators is important for amelioration of circadian rhythms desynchrony, which occurs during shift work, jet lag, aging and depression, and increases the risk of obesity, cardiovascular disease, cognitive deficits, and depression. [unreadable] [unreadable] Because this project focuses on females, the findings will also be relevant to disruptions in circadian hormone rhythms seen in women with affective disorders, such as pre-menstrual dysphoric syndrome, post-partum depression and postmenopausal depression. [unreadable] [unreadable] [unreadable]
|
1 |