In an attempt to better understand the neuroendocrine mechanisms involved in the control of gonadotropin and prolactin secretion in health and disease, we plan to further investigate the inhibitory role of dopamine (DA) and endogenous opiate peptides on gonadotronin release in healthy women and in hypogonadotropic states. Recently, we have presented data suggesting an increased hypothalamic DA and opioid peptides inhibition of gonadotropins during the late follicular and mid-luteal but not the early follicular phase of the menstrual cycle. To determine whether estrogen and/or progesterone modulate the inhibitory effect of endogenous opiates on LRF neuronal activity, we plan to do sequential naloxone infusion in agonadal women with or without exogenous estrogen and/or progesterone administration. To test our hypothesis that a reduction in the excessive DA and/or opioid inhibition of LRF-LH system may be involved in the initiation of the midcycle gonadotropin surge, DA, beta-endorphin or their receptor blockers will be administered mid-cycle to normal cycling women. Previously, we have demonstrated an LH increment following the administration of both DA and opiate receptor antagonists in both patients with hypothalamic hypogonadotropic amenorrhea and those with prolactinoma; however, patients with prepubertal gonadotropin levels failed to respond. To determine whether previous LH non-responders are a distinct neuroendocrine disorder or whether they represent a more severe form of hypogonadotropinism, we plan to repeat naloxone studies after exogenous LRF priming. We then plan to determine the role of endogenous DA and/or opiate peptides in the inhibition of the LRF-LH system in 4 additional hypogonadotropic states: postpartum, post-complete prolactinomectomy, anorexia nervosa and puberty. Finally, we plan to assess whether a DA excess attenuates the pulsatile LH release in prolactinoma patients by monitoring changes in the circulating gonadotropin levels during the infusion of a DA receptor antagonist, metoclopramide.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000827-13
Application #
3090108
Study Section
General Clinical Research Centers Committee (CLR)
Project Start
1974-03-01
Project End
1989-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
13
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
Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451
Lavigne, Katie M; Woodward, Todd S (2018) Hallucination- and speech-specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task-based fMRI data: An fBIRN study. Hum Brain Mapp 39:1582-1595
Milot, Marie-Hélène; Marchal-Crespo, Laura; Beaulieu, Louis-David et al. (2018) Neural circuits activated by error amplification and haptic guidance training techniques during performance of a timing-based motor task by healthy individuals. Exp Brain Res 236:3085-3099
Hsu, Simon; Rifkin, Dena E; Criqui, Michael H et al. (2018) Relationship of femoral artery ultrasound measures of atherosclerosis with chronic kidney disease. J Vasc Surg 67:1855-1863.e1
Inker, Lesley A; Grams, Morgan E; Levey, Andrew S et al. (2018) Relationship of Estimated GFR and Albuminuria to Concurrent Laboratory Abnormalities: An Individual Participant Data Meta-analysis in a Global Consortium. Am J Kidney Dis :
Egnot, Natalie Suder; Barinas-Mitchell, Emma; Criqui, Michael H et al. (2018) An exploratory factor analysis of inflammatory and coagulation markers associated with femoral artery atherosclerosis in the San Diego Population Study. Thromb Res 164:9-14
Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671
Chen, Teresa K; Appel, Lawrence J; Grams, Morgan E et al. (2017) APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension). Arterioscler Thromb Vasc Biol 37:1765-1769
Juraschek, Stephen P; Appel, Lawrence J; Miller 3rd, Edgar R (2017) Metoprolol Increases Uric Acid and Risk of Gout in African Americans With Chronic Kidney Disease Attributed to Hypertension. Am J Hypertens 30:871-875
Chen, Teresa K; Tin, Adrienne; Peralta, Carmen A et al. (2017) APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD. Clin J Am Soc Nephrol 12:1771-1777

Showing the most recent 10 out of 1825 publications