Neuropeptide Y Stimulates the Release of Luteinizing Hormone-Releasing Hormone from Medial Basal Hypothalamus in vitro: Modulation by Ovarian Hormones

Abstract

These studies investigated the effects of neuropeptide Y (NPY) on in vitro release of luteinizing hormone-releasing hormone (LHRH) from the medial basal hypothalmus (MBH) and tested whether ovarian steroids modulate the LHRH response to NPY. Ovariectomized rats were implanted with 20-mm-long Silastic capsules containing a low concentration of estradiol (E₂) (150 µg/ml oil), a high concentration of E₂(250 µg/ml oil), or sesame oil vehicle. Additional animals received high-dose E₂ capsules plus an injection of progesterone (15 mg) concomitantly. Two days later, individual MBH fragments were incubated in medium alone for a 30-min period to obtain the basal rate of LHRH release, followed by a second 30-min period in medium containing NPY or saline. Exposure to NPY (10^–6M) increased the release of LHRH from MBH of ovarian hormone-treated, but not from hormonally untreated rats. The LHRH response was most pronounced from the MBH of rats treated with either high-dose E₂ or E₂ plus progesterone. The increase in LHRHrelease was also elicited by 10^–7M, but not by 10^–8M NPY concentrations, using MBH from E₂ plus progesterone-treated rats. In addition, NPY markedly potentiated the KCl-evoked release of LHRH from MBH of ovariectomized, hormonally untreated or low-dose E₂-treated rats, under conditions when there was little or no effect of NPY on the basal LHRH release. Further, the release of LHRH stimulated by NPY was not accompanied by increase in the release of norepinephrine or of dopamine. These results strongly suggest that the NPY stimulation of LH secretion after intracerebral administration in steroid-primed rats occurs, in part, as a result of increased release of LHRH. NPY may act at the level of the LHRH neurosecretory terminals in the median eminence as well as at additional sites containing LHRH perikarya.

Dynamic Changes in Neuropeptide Y Concentrations in the Median Eminence in Association with Preovulatory Luteinizing Hormone Release in the Rat

“…This assumption is supported by findings that N P Y stimulates LHRH release when added to the hypothalamus in vitro (30) or when slowly infused into the hypothalamus (38). In addition, high levels of NPY detected in the hypophysial portal plasma in the afternoon of proestrus (37) support the suggestion of potentiation by NPY of LHRH action at the level of gonadotrophs (31).…”

“…A rapid rise in the ME NPY concentrations occurred at least one h prior to a rise in serum LH. Because N P Y can rapidly stimulate LH and LHRH release (29)(30)(31), this implies that an accumulation of NPY in the ME nerve terminals not only precedes, but is independent of release of the peptide to fulfil the dual roles (30,31). Further, based on the evidence of a time-lag between accumulation and release of NPY, we propose that M E NPY accumulation is initiated by a distinct neural circuit in anticipation of the impending discharge, which lasts for several hours.…”

“…Coincident with these neural events, and also preceding the LH rise, is an accumulation of LHRH in the median eminence (ME) (14,(16)(17)(18)(19)(20)(21). These neural events in sequential array are interrelated, as prior disruption of either the opioid or adrenergic modulatory influences block the antecedent accumulation and subsequent discharge of hypothalamic L H R H (16, 20, Recently, we observed that another hypothalamic neuropeptidergic system, neuropeptide Y (NPY) (25-28), can stimulate LH and LHRH release in the rat (29)(30)(31)(32). Because NPY coexists with 22-24).…”

“…These neural events in sequential array are interrelated, as prior disruption of either the opioid or adrenergic modulatory influences block the antecedent accumulation and subsequent discharge of hypothalamic L H R H (16, 20, adrenergic transmitters in some of their projections from the brainstem to the preoptic-tuberal pathway (27,28,32), and because NPY acts in the same manner as norepinephrine in affecting LH and LHRH release (29), we hypothesized that NPY may play an important role in stimulation of LH release on proestrus (10,11). NPY has a dual site of action, one in the hypothalamus to excite LHRH release either on its own and/or in a co-action with adrenergic transmitters (30)(31)(32)(33)(34)(35), and the second, at the level of pituitary gonadotrophs to activate and/or potentiate LH release induced by LHRH (31). These observations were recently corroborated by two reports showing that NPY antiserum administered either intraventricularly or systemically blocked the progesterone-induced LH release in ovariectomized rats (36,37).…”

Effects of Chronic Central Nervous System Administration of Agouti-Related Protein in Pair-Fed Animals

“…Acute ICV administration of either NPY or AGRP to intact male rats increased plasma leutinizing hormone (LH) (31,32). Both neuropeptides increased the release of LH-releasing hormone (LHRH) from medial basal hypothalamic explants (31,33). Chronic 7-day administration of NPY resulted in obesity and a dramatic suppression of plasma testosterone, LH, follicle-stimulating hormone (FSH), and seminal vesicle weight, and profoundly inhibited the somatotropic axis (34,35).…”