Research reportLuteinizing hormone and luteinizing hormone-releasing hormone secretion is under locus coeruleus control in female rats
Introduction
The luteinizing hormone (LH) preovulatory surge is the key event in the estrous cycle. Its release depends on hypothalamic luteinizing hormone releasing hormone (LHRH) secretion from nerve terminals into the median eminence (ME) [29]. Ovarian steroids classically control LHRH and LH secretion by positive and negative feedback [35] but the precise mechanisms by which estradiol (E2) and progesterone (P) exert their effects are not completely established.
Since either E2[43] or α-estradiol receptors (αER) [17] are not co-localized in the LHRH neurons, it has been suggested that the estrogen influence on LHRH secretion occurs by indirect mechanisms. On the other hand, recent studies demonstrated the expression of β-estradiol receptors (βER) in LHRH neurons in rodents [23]. However, since there was no difference in the number of βER immunoreactive neurons between female rats in different hormonal states and male rats, the βER expression seems not to be steroid-dependent. It is possible that these receptors could be involved in the negative feedback mechanism, since they can exert opposite effects to αERs [32]. According to this result, it seems reasonable to consider that the positive feedback could be exerted by indirect actions of E2 modulating neurotransmitter secretion.
Its well known that one of the major neurotransmitters that controls LH secretion is norepinephrine (NE). The NE turnover in the preoptic area parallels changes in circulating LH concentrations [21]. Moreover, direct infusion of NE as well as methoxamine, an α1-adrenergic agonist, into the ME stimulates LHRH secretion [47] whereas administration of an α1-adrenergic antagonist eliminates the preovulatory LH surge [27] and the one induced by sexual steroids in ovariectomized rats [8].
The noradrenergic innervation of the hypothalamus is extrinsic [38] and comes from terminals originating in cell bodies located in the brain stem. The locus coeruleus (LC) is the major noradrenergic nucleus and has extensive efferent projections throughout the entire central nervous system (CNS) [14], [46] including areas involved in LH and LHRH synthesis and release [10].
Electrical stimulation of the LC in ovariectomized rats treated with E2 amplifies the LH surge induced by electrochemical stimulation of the medial preoptic nucleus [12] while electrolytic lesions of the LC block the preovulatory surge of LH [2], [11]. This blockade of LH surge is accompanied by a decrease in the NE content in the medial preoptic area (MPOA) and medial basal hypothalamus (MBH) [2].
These findings strongly suggest that NE from the LC plays an important role mediating the positive feedback action of E2 on LH secretion. However, the role of LC in basal LH secretion has not been studied. Thus, the aim of this study was to evaluate the effect of LC lesion on basal LH secretion, which occurs during metestrus, diestrus and estrus as well as on the LH surges in the afternoon of proestrus and in ovariectomized rats treated with E2 and progesterone (OVXE2P). Also, by measuring LHRH content in the cell bodies of the MPOA, as well as in the terminals in the ME, we investigated whether the effects of LC lesion on LH secretion might be due to alterations in LHRH secretion.
Section snippets
Animals
Adult female Wistar rats weighing 250–300 g from the animal house of the Ribeirão Preto Campus of the University of São Paulo were maintained under controlled lighting (lights on from 06:00 to 18:00 h) and temperature (24±0.5 °C). Food (standard rat chow, Nuvilab) and tap water were provided ad libitum.
Experimental design
Experiment I examined the effect of LC lesion on LH and LHRH secretion during the estrous cycle. Experiment II examined the effect of LC lesion on LH and LHRH secretion in ovariectomized rats
Results
Most of the missed lesions were located posterior to the LC. However, there were lesions dislocated to the right (lateral to the LC on the right side and medial on the left side) or to the left (lateral to LC on the left side and medial on the right side) and a few of them were also located dorsal to the LC (Fig. 1A, left). The size of the missed lesions did not differ from that of successful lesions. A complete lesion of the LC is shown in Fig. 1A (right). Fig. 1B shows the photomicrographic
Discussion
The present data demonstrate that LC lesion did not modify LHRH content or basal plasma LH during metestrus, diestrus and estrus; however, it completely abolished the preovulatory LH surge in proestrus, as well as the one induced by gonadal steroids in ovariectomized rats. These blockades were accompanied by an increased content of LHRH in the MPOA and ME.
Since lesions located laterally, medially, dorsally or posteriorly to the LC did not block the preovulatory surge, one may hypothesize that
Acknowledgements
We are grateful to Rute Ap. Freitas Marcon and Sonia M. Zanon Baptista for technical assistance, and to Fabricio Viviani for his help. Financial support: FAPESP; CNPq.
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