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(Z)‐Bisdehydrodoisynolic Acid (BDDA), a Non‐Steroidal Uterotrophic and Potentially Neuroprotective Compound in Brain Injury, Induces Proestrus‐like Luteinizing Hormone Secretion and Lordosis Behavior in Ovariectomized Female Rats
Author(s) -
Clough Rich W.,
Viscomi Natalie S.,
Arbogast Lydia,
Hou Yuqing,
Banz William J.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.744.6
Subject(s) - ovariectomized rat , medicine , endocrinology , luteinizing hormone , estradiol benzoate , lordosis behavior , hormone , lordosis , traumatic brain injury , endocrine system , estrous cycle , radiography , radiology , psychiatry
Exploring therapeutic interventions in experimental Traumatic and Concussive Brain Injury (TBI, CBI) in rodents, we have previously reported that (Z)‐BDDA, a non‐steriodal but estrogenic compound of interest, significantly improved the rate and extent of behavioral improvement in rats subject to lateral fluid percussion brain injury (an experimental model of TBI). Z‐BDDA is a synthetic compound described as highly estrogenic based on uterotrophic activity in female rats. Estrogenicity in brain has not been established. Insofar as the effects of Z‐BDDA on TBI may be due to an “estrogenic” effect in brain, we sought to determine whether the compound does indeed have estrogenic effects on this organ. Accordingly, we explored the induction of Luteinizing Hormone (LH) secretion and lordosis behavior using a standardized priming model in ovariectomized (OVX) female rats. Female Sprague‐Dawley rats were OVXed under isofluorane anesthesia and assigned to various steroid treatment protocols intended to induce (preovulatory‐like) LH secretion sexual receptivity. Z‐BDDA (300 or 30 Ug/rat) or Estradiol Benzoate (EB, 10 ug/rat) was administered (sc) two weeks following OVX and some rats were also given progesterone (1mg/rat) 48 hours later. Lordosis behavior was assessed (at onset of dark‐phase) by placement in an arena containing a sexually mature male rat. Mount attempts by the male and lordotic responses in females were recorded to obtain a lordosis quotient. For endocrine studies, rats were treated as with the behavioral studies, but at onset of dark were euthanized and blood was collected immediately for LH measurement by radioimmunoassay. Our results confirmed a profound estrogenic effect of Z‐BDDA on both LH secretion and lordosis responding in female rats. Compared to control groups, Z‐BDDA was equipotent to EB in this priming model. Estrogenic compounds have shown high promise in the experimental brain injury literature but the use of estrogens per se, in the human context, is controversial. This warrants continued research with other compounds, such as Z‐BDDA, that are estrogenic and also have a variety of other attributes potentially beneficial in brain injury but that avoid the confounds of estrogen. Support or Funding Information Supported by SIU School of Medicine and the SIUC Neuroscience Research Center.