Fos Expression by Naloxone in LHRH Neurons ofthe Mediobasal Hypothalamus and Effects of Pentobarbital Sodium in the Proestrous Rat

Abstract

Because Fos is thought to be induced in neurons that are activated, we examined whether luteinizing hormone-releasing hormone (LHRH) neurons expressed Fos protein when they were stimulated by an opioid receptor antagonist naloxone (NAL), expecting to identify LHRH neurons which are regulated by opioid neurons directly or indirectly. Further, we examined whether an ovulation-blocking dosage of pentobarbital sodium (PB) would affect the NAL-induced Fos expression. Female rats were infused with naloxone (5 mg/kg/h) for 90 min (10.00-11.30) in the morning of proestrus, during which infusion blood sampling was done, and were killed by i.v. injection with an overdose of PB at 11.30-12.00. Dual immunoperoxidase/immunofluorescence staining for both Fos and LHRH revealed that some LHRH immunoreactive (ir) neurons in the forebrain expressed Fos-ir, associated with an increase in serum LH concentrations, but little co-localization was found in rats in proestrus which were infused with saline as the control. The proportion of LHRH-ir neurons which expressed Fos-ir was about 35-62% in the caudal part of the forebrain including the mediobasal hypothalamus, and this was larger than that (10%) in the rostral part of the forebrain including the preoptic area. PB injection (32 mg/kg bw, i.p.) 15 min prior to the beginning of NAL infusion significantly enhanced the increase in LH secretion due to NAL, and also enhanced Fos-ir expression in LHRH-ir neurons. Together with the well-established fact that PB blocks the LHRH surge generator and our previous findings that NAL stimulates the LHRH pulse generator even in the PB-blocked proestrous rat, these results strongly suggest that the LHRH pulse generator exists in the mediobasal hypothalamus which contains LHRH neurons that are responsive to NAL and express Fos protein.

A Subset of Gonadotropin-Releasing Hormone Neurons in the Ovine Medial Basal Hypothalamus Is Activated during Increased Pulsatile Luteinizing Hormone Secretion1

“…They are thus consistent with the hypothesis that stimulation of pulsatile GnRH secretion by these agents involves a subset of GnRH neurons located in the MBH. Similar results have recently been reported in the rat, where naloxone has been shown to increase the percentage of GnRH cells expressing Fos in the lateral hypothalamic area, the most caudal portion of their distribution (38). While neural systems can be activated without concomitant Fos/FRA expression (37), the association of the two is sufficiently common that Fos/FRA expression is now generally accepted as an indication of an increase in neural activity (23,24).…”

Control of puberty onset and fertility by gonadotropin-releasing hormone neurons

“…Whether all of these hypophysiotropic GnRH neurons, or just a subpopulation, are involved in the pulsatile secretion of GnRH is unclear. Studies undertaken in rodents suggest that <100 GnRH neurons are sufficient for pulsatile LH secretion [25][26][27] and that the most caudally positioned GnRH neuron cell bodies might be preferentially involved in pulse generation 28,29 .…”

Role of Gamma-Aminobutyric Acid Neurons in the Release of Gonadotropin-Releasing Hormone in Cultured Rat Embryonic Olfactory Placodes

“…Since it has been shown that a very small number of GnRH neurons, i.e., a total of about 20 neurons, in the mediobasal hypothalamus [73, 74, 75, 76, 77]generate pulsatile GnRH release [78, 79, 80, 81, 82], and only 10–20 neurons are able to produce volleys of multiunit activity, each revealing the GnRH secreting activity of the GnRH pulse generator [83], the activity of the majority of GnRH neurons, probably more than 400 neurons [77, 84], would be overlooked at least in ordinary culture conditions. Even so, it is necessary to more definitely differentiate two subgroups of GnRH neurons in our olfactory placode cultures.…”