The sex hormone progesterone has been shown to improve outcomes in animal models of a number of neurologic diseases, including traumatic brain injury, ischemia, spinal cord injury, peripheral nerve injury, demyelinating disease, neuromuscular disorders, and seizures. Evidence suggests it exerts its neuroprotective effects through several pathways, including reducing edema, improving neuronal survival, and modulating inflammation and apoptosis. In this review, we summarize the functional outcomes and pathophysiologic mechanisms attributed to progesterone treatment in neurologic disease. We then comment on the breadth of evidence for the use of progesterone in each neurologic disease family. Finally, we provide support for further human studies using progesterone to treat several neurologic diseases.
Objective: To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Design: Randomized controlled trial. Setting: Clinical research center at an academic medical university. Patient(s): Seventeen women with FHA were randomized either to CBT or observation. Intervention(s): CBT versus observation. Main Outcome Measure(s): Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T 3 ), and total and free thyroxine (T 4 ) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Result(s): Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T 3 , or T 4 levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T 3 and T 4 remained unchanged. Conclusion(s): In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA.
In the normal rodent breast, the pineal hormone melatonin controls the development of ductal and alveolar tissue. Melatonin counteracts tumor occurrence and tumor cell progression in vivo and in vitro in animal and human breast cancer cell cultures. It acts predominantly through its melatonin MT1 receptor. Our aim was to investigate the presence or absence of the MT1 melatonin receptor in the aggressive triple negative group of human breast carcinoma (TNBC) and its possible relationship to the course of the disease. A total of 167 patients with a ER-, PR-, Her-2/neu- phenotype in which tissue for receptor studies was available were examined. The MT1 receptor immunostain was evaluated semiquantitatively as staining intensity (0, 1, 2, 3), percentage of stained cells and the weighted index (WI) (staining intensity times percentage of stained cells). A score of WI < 60 was regarded as "negative". There was a striking difference in incidence of MT1 positivity and staining intensity between carcinomas in African American (AA) and Caucasian (C) women. The AA showed a higher incidence of MT1 negative tumors (41/84 = 48.8 % in AA, 6/51 = 11.8 % in C) and a lower average WI. MT1 positivity in TNBC was associated with a lower stage and a smaller tumor size at time of diagnosis. In multivariable survival analysis, MT1 negative TNBC in all cases regardless of race showed a significantly higher hazard ratio for disease progression, shorter progression free survival, and disease-related death, and shorter OS. This was especially pronounced in the AA group but did not reach statistical significance in the smaller group of C alone. These results suggest that melatonin or a melatonin receptor agonist may be useful biologic additions in the treatment of some forms of TNBC, especially in AA who generally show a more aggressive course of their disease.
Background: NR5A nuclear receptors are important pharmaceutical targets with poorly understood ligand regulation. Sequence divergence has potentially altered their ligand response in model organisms.
Results: Sequence divergence has differentially impacted ligand binding and protein dynamics in NR5A orthologs.
Conclusion: Mouse LRH-1 is a phospholipid-responsive receptor, whereas Drosophila NR5A2 is not.
Significance: Mice are viable therapeutic models for LRH-1-dependent diseases.