Paraventricular .ALPHA.1- and .ALPHA.2-Adrenergic Receptors Mediate Hindbrain Lipoprivation-induced Suppression of Luteinizing Hormone Pulses in Female Rats

Abstract

Abstract. Acute central lipoprivation suppresses pulsatile luteinizing hormone (LH) release and increases blood glucose levels through noradrenergic input to the hypothalamic paraventricular nucleus (PVN) in female rats. The present study was conducted to identify adrenergic receptor subtypes involved in central lipoprivation-induced suppression of pulsatile LH secretion and increases in plasma glucose levels in female rats. Acute hindbrain lipoprivation was produced by injection into the fourth cerebroventricle (4V) of 2-mercaptoacetate (MA), an inhibitor of fatty acid oxidation, in estradiol-implanted ovariectomized rats. Two min before MA injection, α1-, α2-or β-adrenergic receptor antagonist was injected into the PVN. Injection of MA into the 4V suppresses pulsatile LH release in PVN vehicle-treated rats, whereas pretreatment of animals with injection of α1-or α2-adrenergic antagonist into the PVN blocked the effect of the 4V MA injection on LH pulses. β-Adrenergic antagonist did not affect MA-induced suppression of LH pulses. The counter-regulatory increase in plasma glucose levels after 4V MA injection was also partially blocked by pretreatment with α1-and α2-adrenergic receptor antagonists. These results suggest that α1-and α2-adrenergic receptors in the PVN mediate hindbrain lipoprivation-induced suppression of LH release and counterregulatory increases in plasma glucose levels in female rats. Key words: Adrenergic receptor, Energy sensing, Free fatty acid, Lipoprivation, Mercaptoacetate, Rat (J. Reprod. Dev. 54 : 198-202, 2008) nergy availability is one of the critical factors regulating gonadal function through control of gonadotropin release in mammals at various phases of reproduction, such as the onset of puberty and lactational anestrus [1][2][3][4]. Pulsatile luteinizing hormone (LH) release is suppressed by food restriction or acute food deprivation in rats [1,5,6]. Acute glucoprivation induced by peripheral injection of 2-deoxyglucose (2DG) also results in suppression of LH pulses [7].Glucose availability has been reported to be monitored by a specific sensor(s) located in the brain to regulate food intake [8]. The hindbrain may monitor glucose availability in rats to control food intake and LH release because 2DG injection into the fourth cerebroventricle (4V) increases food intake and suppresses LH release [9]. Glucokinase-immunoreactive ependymocytes in the hindbrain show an in vitro increase in intracellular Ca 2+ levels in response to altered extracellular glucose levels [10], suggesting that ependymocytes in the hindbrain play a role in glucose sensing. In addition, information concerning the glucose availability may partly be conveyed by noradrenergic ascending input into the hypothalamic paraventricular nucleus (PVN) [11].Peripheral and central inhibition of β-oxidation of fatty acids, another metabolic fuel, also suppresses pulsatile LH release in female rats [12,13], suggesting that the fatty acid is a metabolic signal controlling LH release. Our previous study demonstrated that fat...

Food Deprivation Induces Monocarboxylate Transporter 2 Expression in the Brainstem of Female Rat

“…Glucose sensing by the hindbrain is thought to be of particular importance in suppression of LH secretion under negative energy balance [4,5]. It is also possible that other oxidizable fuels, such as fatty acids [6,7] and ketone bodies [8], serve as metabolic signals informing the brain of nutritional conditions to induce LH suppression.Ketone bodies are produced in the liver from excess amounts of acetyl-CoA under malnutritional conditions. Under such circumstances, glucose utilization in the brain decreases, while uptake of ketone bodies into the brain increases [9][10][11].…”

Central Injection of Ketone Body Suppresses Luteinizing Hormone Release via the Catecholaminergic Pathway in Female Rats

“…Local PVN injection of α1-or α2-adrenergic receptor agonists suppressed pulsatile LH release in female rats [10]. Lipoprivic suppression of LH pulses is rescued by pretreatment with α1-or α2-adrenergic receptor antagonists in the PVN [25]. Thus, PVN α1-or α2-adrenergic receptor may be associated with the suppressed gonadotropin release under decreased energy availability.…”

“…Numerous studies have indicated that the brain energy sensor resides within the hypothalamus and brainstem [18][19][20][21][22][23]. Previous studies have raised the possibility that brainstem energy sensors sense glucose and fatty acid availability to regulate gonadotropin secretion because administration of 2-deoxyglucose (2DG), a competitive inhibitor of glucose oxidation, or mercaptoacetate (MA), an inhibitor of fatty acid oxidation, into the fourth cerebroventricle (4V) suppresses LH pulses in rats [12,24,25]. Likewise, blockade of hindbrain monocarboxylate transporter 1 (MCT1), a ketone body transporter located in ependymocytes around the 4V, results in normalization of diabetic hyperphagia in rats [26].…”

“…To this end, the effect of 3HB injection into the 4V on pulsatile LH secretion was examined in female rats to investigate whether ketone bodies sensed by the hindbrain energy sensor act as a negative signal. We also examined whether noradrenergic inputs to the hypothalamic paraventricular nucleus (PVN) are associated with 3HB-induced pulsatile LH suppression because our previous studies showed that glucoprivic suppression of pulsatile LH suppression was mediated by noradrenergic inputs to the PVN [11] and that lipoprivation also suppressed pulsatile LH secretion via the PVN noradrenergic pathway [12,25]. …”

“…Thus, ketone bodies may be associated with the inhibition of glucose metabolism in ependymocytes to sense the level of energy substrates. Further studies are required to address these points.Previous studies suggested that LH pulse suppression caused by malnutrition, such as fasting [9], glucoprivation [11] or lipoprivation [12,25], is mediated by noradrenergic neurons projecting to the PVN. Local PVN injection of α1-or α2-adrenergic receptor agonists suppressed pulsatile LH release in female rats [10].…”