Diurnal and estradiol-dependent changes in gonadotropin-releasing hormone neuron firing activity

Abstract

A robust gonadotropin-releasing hormone (GnRH) surge is a prerequisite signal for the luteinizing hormone (LH) surge that triggers ovulation. In rodents, the GnRH surge is initiated by elevated estradiol and a diurnal switch in estrogen action from negative to positive feedback. The ability of constant estradiol treatment to induce daily LH surges was tested in adult mice that were ovariectomized (OVX) or OVX and treated with estradiol implants (OVX؉E). LH in OVX mice showed no time-of-day difference. In contrast, OVX؉E mice showed a large LH surge (8-to 124-fold relative to the a.m.) in p.m. samples on d 2-5 post-OVX؉E. Targeted extracellular recordings were used to examine changes in firing activity of GnRH neurons in brain slices. There was no time-of-day difference in cells from OVX mice. In contrast, OVX؉E cells recorded in the p.m. showed an increased mean firing rate and instantaneous firing frequency, which could increase GnRH release, and decreased duration of quiescence between bouts of firing, possibly reflecting increased pulse frequency, compared with cells recorded in the a.m. In the a.m., OVX؉E cells showed changes in GnRH neuron firing reflecting negative feedback compared with OVX cells, whereas in the p.m., OVX؉E cells exhibited changes suggesting positive feedback. These data indicate that differences in pattern and level of individual GnRH neuron firing may reflect the switch in estradiol action and underlie GnRH surge generation. The persistence of altered GnRH neuron activity in slices indicates that this approach can be used to study the neurobiological mechanisms of surge generation.luteinizing hormone ͉ mouse model ͉ surge ͉ electrophysiology ͉ neuroendocrinology

Gonadotropin-Releasing Hormone Neurons Express KATPChannels That Are Regulated by Estrogen and Responsive to Glucose and Metabolic Inhibition

“…As expected, the uterine weights of the E2-treated group (152 Ϯ 10.5 mg) were significantly greater than the uterine weight of the oil-treated group (21 Ϯ 1.4 mg), indicative of the circulating levels of estrogen (Christian et al, 2005). However, neither Kir6.2 nor SUR1 mRNA expression was altered with estrogen treatment (Fig.…”

“…In addition, female mice used for the scPCR and real-time PCR were either intact or ovariectomized, implanted with oil or E2 capsules, and given a single injection of oil (100 l) or estradiol benzoate (EB) (2 g in 100 l of oil, which yields plasma E2 levels of ϳ75 pg/ml) 24 h before the experiment. The animals were killed at 10:00 A.M. during negative feedback (Christian et al, 2005). This supplemental estrogen treatment was used to increase mRNA expression, although it did not alter the E2-induced current.…”

Prostaglandin E 2 release from astrocytes triggers gonadotropin-releasing hormone (GnRH) neuron firing via EP2 receptor activation

“…Previous studies have shown that GnRH firing activity is modified by estradiol in a diurnal-dependent manner (47), and that COX-2 expression in the preoptic region is greater in males than females (48). Perhaps the lack of changes in GnRH firing activity is related to the fact that all recordings were made at the same time of day and using a saturating dose of PGE 2 .…”

The Role of Kisspeptin–GPR54 Signaling in the Tonic Regulation and Surge Release of Gonadotropin-Releasing Hormone/Luteinizing Hormone

“…The purpose of this experiment was to test the model that GPR54 signaling mediates the positive feedback effects of E on LH secretion. To accomplish this, we used a protocol that was previously shown to induce a daily, evening LH surge in mice (Christian et al, 2005). Adult female WT and GPR54 KO mice were subjected to the LH surge protocol as described below.…”

“…We used the protocol devised by Christian et al (2005) to induce a predictably timed LH surge in adult female mice. Briefly, on the morning of day 0, mice were anesthetized by inhaled isofluorane, and the ovaries were removed through bilateral incisions.…”