Submission Number: GRE-4-20-7

Abstract Number: 1

A SITE OF ACTION FOR ESTRADIOL SUPPRESSION OF LH SECRETION VIA DOPAMINERGIC NEURONS IN THE ANESTROUS EWE.

Greg M Anderson*, John M Connors, Steve L Hardy, Miroslav Valent and Robert L Goodman*

Department of Physiology, West Virginia University, Morgantown, WV ¹

Abstract:
Estradiol (E) exerts negative feedback on GnRH/LH secretion in the anestrous ewe via A15 dopaminergic (DA) neurons. Since these neurons do not possess the estrogen receptor- (ER), we hypothesized that ER-containing neurons in the ventromedial preoptic area (POA), which are known to be activated by s.c. E implants, may be the initial step in a neuronal system involving dopamine whereby E suppresses GnRH secretion. To test this, 3 experiments were conducted using ovariectomized ewes receiving either empty or E-containing bilateral 22 G tubular implants lowered via stereotaxically placed guide tubes to the POA (POA blank and POA E groups) or s.c. 30 mm silicone rubber E-containing implants (s.c. E group). In Exp. 1, LH pulse frequency was measured for 4 h on days 0, 1, 7 and 14 of implant treatment during anestrus. In POA E (n = 4) and s.c. E (n = 5) groups, mean LH pulse frequency (1.8 0.5 and 0 pulses/4 h respectively) was suppressed on day 7 compared to pretreatment values (4.3 0.5 and 3.6 0.5 pulses/4 h; P < 0.01), whereas no suppression was evident in POA blank (n = 3) ewes (day 0: 3.7 0.9; day 7: 4.0 0.3 pulses/4 h). In Exp. 2, this protocol was repeated during the breeding season. LH pulse frequency did not change between days 0 and 7 in any of POA E (n = 6), POA blank (n = 4) or s.c. E (n = 5) groups (P > 0.05). Exp. 3 tested if the effect of 7 d of E in anestrus could be overcome by a DA-D₂ receptor antagonist by comparing LH pulse frequencies before and after a bolus injection of (-)-sulpiride (1.2 mg/kg) in POA E (n = 9), POA blank (n = 6) and s.c. E (n = 5) ewes. E (but not blank) implant treatment again suppressed LH pulse frequency (P < 0.001) and this was reversed by sulpiride in POA E ewes (before injection: 1.6 0.5 pulses/4 h; after injection: 2.9 0.5 pulses/4 h; P < 0.01). We conclude that E acts on cells in the POA to activate a system involving DA neurons to suppress GnRH/LH pulsatility in the anestrous ewe. Supported by NIH-HD17864. .

Keywords: estrogen negative feedback, dopamine, anestrus

This abstract is being presented at: 1:30 PM in session:
SESSION I: TRAINEE RESEARCH COMPETITION