Effects of Electrical Stimulation of the Medial Basal Hypothalamus on thein VivoRelease of Luteinizing Hormone-Releasing Hormone in the Prepubertal and Peripubertal Female Monkey*

Abstract

In this study the hypothesis that the LHRH neurosecretory system of the prepubertal female monkey has the capacity to function in a manner comparable to that of monkeys in more mature stages of development was tested. Using push-pull perfusion in the stalk-median eminence, effects of electrical stimulation of the medial basal hypothalamus on in vivo LHRH release were determined in conscious prepubertal, early pubertal, and midpubertal monkeys. After a 180-min period of baseline sample collection, electrical stimulation was applied six times at 90-min intervals via a monopolar electrode, the tip of which was 1-2 mm rostro-dorsal to the perfusion site. Control experiments were performed in the same manner, but without electrical stimulation. During control perfusions, the mean LHRH level remained stable. Mean (+/- SEM) LHRH release for the entire perfusion period in control experiments was 0.5 +/- 0.2, 2.4 +/- 0.4, and 2.2 +/- 0.7 pg/ml.10 min for the prepubertal (n = 6), early pubertal (n = 4), and midpubertal (n = 6) groups, respectively. Mean LHRH release in the prepubertal group was significantly lower than that in either of the older groups (P less than 0.05). In contrast, in all three age groups, repeated electrical stimulation of the medial basal hypothalamus resulted in 1) a short latency increase in LHRH release occurring within 20 min after each stimulation, and/or 2) a gradual increase in mean LHRH release over several hours. In the prepubertal group (n = 4), mean LHRH levels were 0.8 +/- 0.5 pg/ml.10 min during the 90 min before the first electrical stimulation and increased to 6.1 +/- 2.9 pg/ml.10 min during the 90 min after the sixth stimulation. This degree of responsiveness was similar to that of the older age groups. Mean LHRH levels before stimulation were 1.3 +/- 0.6 and 2.4 +/- 1.1 pg/ml.10 min in the early pubertal (n = 5) and midpubertal (n = 5) groups, respectively, and increased to 7.8 +/- 3.5 and 6.0 +/- 1.8 pg/ml.10 min, respectively, after the sixth stimulation. These increases in LHRH concentration with electrical stimulation were significant for all three age groups (P less than 0.03-0.001), while there were no significant differences between age groups. The temporal patterns of these responses suggest that electrical stimulation elicits LHRH release with a similar magnitude in all three age groups by 1) depolarizing LHRH neurons directly, and/or 2) stimulating multineuronal systems that synapse with LHRH neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuroendocrine mechanism of onset of puberty. Sequential reduction in activity of inhibitory and facilitatory N-methyl-D-aspartate receptors.

“…The occurrence ofepisodic increase in GnF ing a static incubation system is unlikely to re ological artefact because these episodic change, by changes in culture conditions such as calciun nesium and glycine concentrations ( 15,23). ] changes in episodic GnRH secretion that we such as increase in frequency at onset of pubertj with data obtained in vivo (7)(8)(9)(10). Finally, l search was a continuation ofprevious studies, il to work in similar conditions for the presen Nonetheless, a possible influence ofthe samplir of the occurrence ofGnRH pulses using the static incubation sys-/1…”

“…In the hypothalamus, GnRH is secreted in a pulsatile manner driven by a pacemaker system or pulse generator (4)(5)(6). In different species, the onset ofpuberty is characterized by an increased frequency of pulsatile GnRH secretion (7)(8)(9)(10). We have particularly studied the male rat which is prepubertal at 15 d of age.…”

gamma-Aminobutyric acid is an inhibitory neurotransmitter restricting the release of luteinizing hormone-releasing hormone before the onset of puberty.

“…However, the mechanism by which LHRH release increases at puberty in primates is still unknown. The pubertal increase in LHRH release is probably not due to the developmental changes in properties of LHRH neurons themselves, since (i) the expression of LHRH mRNA is similar in monkeys during the prepubertal period and in adulthood (5) and (ii) prior to puberty, LHRH release can be induced by electrical stimulation of the medial basal hypothalamus (MBH) (2) or by neurochemical stimulation with N-methyl-D-aspartate (6). In fact, these studies further indicate that releasable LHRH is present in the hypothalamus of prepubertal monkeys but that the control mechanisms for pulsatile LHRH release are immature before the onset of puberty.…”

An increase in in vivo release of LHRH and precocious puberty by posterior hypothalamic lesions in female rhesus monkeys (Macaca mulatta)

“…Similarly, electrical stimulation of the basal hypothalamus in female prepubertal monkeys, where LHRH neuroterminals are concentrated, results in an elevation of LHRH release (8). However, stimulation of the LHRH neuronal system directly or indirectly through excitation of upstream regulatory systems may not provide answers to the precise mechanism of the onset of puberty in primates.…”