The overall aim of this proposal is to gain insight into the neuroendocrine factors associated with the occurrence of hypothalamic amenorrhea. This is a heterogeneous syndrome, in which several types of patients with three contributing lifestyle variables may be identified: 1) exericse, 2) nutritional deprivation, and 3) depression. We hypothesize that in all these cases inputs to the GnRH pulsatile secretory mechanism have been modified with a resulting failure of normal pituitary release of gonadotropin. We further propose that the modification in hypothalamic-pituitary function may involve an alteration of pulsatile and circadian hormone release and an altered set-point of the stress system involving CRF, ACTH and related peptides and cortisol. Differences in these modifications are anticipated in different types of hypothalamic amenorrhea associated with the lifestyle variables outlined above. We intend to define such differences in Three Stages of descriptive and experimental observations. FIRST, we propose to screen prospective subjects for their ovulatory, physical, dietary, and psychological status to properly select and assign them to experimental groups. SECOND, we propose to differentiate the 24-hour hormonal rhythms associated with the lifestyle variables and their interactions. THIRD, we propose to conduct four experiments to identify the neuroendocrine mechanisms responsible for the observed 24-hour hormonal rhythms. We will investigate how the lifestyle variables are associated with altered hypothalamic-pituitary mechanisms involving 1) CRF, 2) endogenous opioids, 3) dopamine, and 4) the amino acid neurotransmitter precursors tyrosine and tryptophan. These observations may provide valuable clinical and pathophysiological information concerning the influences of lifestyle on reproduction.

Project Start
1985-12-01
Project End
1990-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Erden, H F; Zwain, I H; Asakura, H et al. (1998) Corticotropin-releasing factor inhibits luteinizing hormone-stimulated P450c17 gene expression and androgen production by isolated thecal cells of human ovarian follicles. J Clin Endocrinol Metab 83:448-52
Laughlin, G A; Dominguez, C E; Yen, S S (1998) Nutritional and endocrine-metabolic aberrations in women with functional hypothalamic amenorrhea. J Clin Endocrinol Metab 83:25-32
Laughlin, G A; Yen, S S (1997) Hypoleptinemia in women athletes: absence of a diurnal rhythm with amenorrhea. J Clin Endocrinol Metab 82:318-21
Cagnacci, A; Soldani, R; Yen, S S (1997) Contemporaneous melatonin administration modifies the circadian response to nocturnal bright light stimuli. Am J Physiol 272:R482-6
Dominguez, C E; Laughlin, G A; Nelson, J C et al. (1997) Altered binding of serum thyroid hormone to thyroxine-binding globulin in women with functional hypothalamic amenorrhea. Fertil Steril 68:992-6
Cagnacci, A; Soldani, R; Yen, S S (1997) Melatonin enhances cortisol levels in aged women: reversible by estrogens. J Pineal Res 22:81-5
Asakura, H; Zwain, I H; Yen, S S (1997) Expression of genes encoding corticotropin-releasing factor (CRF), type 1 CRF receptor, and CRF-binding protein and localization of the gene products in the human ovary. J Clin Endocrinol Metab 82:2720-5
Cagnacci, A; Soldani, R; Laughlin, G A et al. (1996) Modification of circadian body temperature rhythm during the luteal menstrual phase: role of melatonin. J Appl Physiol 80:25-9
Laughlin, G A; Yen, S S (1996) Nutritional and endocrine-metabolic aberrations in amenorrheic athletes. J Clin Endocrinol Metab 81:4301-9
Cagnacci, A; Soldani, R; Yen, S S (1995) Hypothermic effect of melatonin and nocturnal core body temperature decline are reduced in aged women. J Appl Physiol 78:314-7

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