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J C Thiéry

Publications and source records attributed to J C Thiéry.

At least 19 recordsLinked to original sources
PubMed2003

Passage of progesterone into the brain changes with photoperiod in the ewe.

In this study we tested the hypothesis that photoperiod can modulate steroid access to the brain in a seasonal breeder. To this goal, we compared the passage of exogenous progesterone to the brain of female sheep maintained under short (SD) or long (LD) daylengths. In the first experiment, we studied two groups of ovariectomized females maintained under SD or LD, for three artificial cycles, consisting of bearing a subcutaneous oestradiol implant (E2-treated) and an intravaginal device releasing progesterone (CIDR). During the third cycle, the concentrations of progesterone and of its metabolites 5alpha-dihydroprogesterone and 3alpha-hydroxy-5alpha-pregnan-20-one were measured in the preoptic area (POA). The levels of progesterone in the POA were higher in ewes under LD than under SD while the amounts of metabolites were unchanged. In the second experiment, we compared ovariectomized female sheep equipped with a cannula in the third ventricle to sample the cerebrospinal fluid (CSF) under LD vs. SD. After progesterone (1 mg and 10 mg) was injected into the carotid artery, it was only detectable in the cerebrospinal fluid in sheep under LD. In the third experiment, we compared progesterone concentration in plasma and CSF in two groups of SD vs. LD ovariectomized E2-treated ewes for 2 h under CIDR treatment. Despite similar progesterone plasma concentrations, concentration in the CSF was 2.5 times higher in SD than in LD. Our results suggest a physiological modulation of the passage of progesterone to the brain according to the photoperiod.

Animals↗
PubMed2002

Neuroendocrine interactions and seasonality.

Sheep in temperate latitudes are seasonal breeders. Of the different seasonal cues, photoperiod is the most reliable parameter and is used by animals as an indication of the time of the year to synchronize endogenous annual rhythms of reproduction and physiology. The photoperiodic information is transduced into neuroendocrine changes through variations in melatonin secretion from the pineal gland. Melatonin triggers variations in the secretion of luteinizing hormone-releasing hormone, luteinizing hormone and follicle stimulating hormone (LHRH/LH/FSH) responsible for seasonal changes in reproductive activity. In female sheep, the seasonal changes in the hormonal LH pattern mainly reflect an increase in the negative feedback exerted by estradiol under long days on the frequency of pulsatile LH secretion. The resulting seasonal inhibition of LH secretion involves the activation of monoaminergic and especially dopaminergic systems by estradiol. Other types of physiological regulation subject to seasonal changes such as voluntary food intake (VFI), fat metabolism, body mass and pelage growth also occur in sheep, goats or related wild species. Several neuroendocrine intermediates seem to be shared by these different systems and may participate in their synchronization, providing the advantage that this helps mammalian species to adapt to their environment.

Animal Nutritional Physiological Phenomena↗
PubMed2000

Neuronal projections to the lateral retrochiasmatic area of sheep with special reference to catecholaminergic afferents: immunohistochemical and retrograde tract-tracing studies.

The retrochiasmatic area contains the A15 catecholaminergic group and numerous monoaminergic afferents whose discrete cell origins are unknown in sheep. Using tract-tracing methods with a specific retrograde fluorescent tracer, fluorogold, we examined the cells of origin of afferents to the retrochiasmatic area in sheep. The retrogradely labeled cells were seen by observation of the tracer by direct fluorescence or by immunohistochemistry with specific antibodies raised in rabbits or horses. Among the retrogradely labeled neurons, double immunohistochemistry for tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin were used to characterize catecholamine and serotonin FG labeled neurons. The retrochiasmatic area, which included the A15 dopaminergic group and the accessory supraoptic nucleus (SON), received major inputs from the lateral septum (LS), the bed nucleus of the stria terminalis (BNST), the thalamic paraventricular nucleus, hypothalamic paraventricular and supraoptic nuclei, the perimamillary area, the amygdala, the ventral part of the hippocampus and the parabrachial nucleus (PBN). Further, numerous scattered retrogradely labeled neurons were observed in the preoptic area, the ventromedial part of the hypothalamus. the periventricular area, the periaqueductal central gray (CG), the ventrolateral medulla and the dorsal vagal complex. Most of the noradrenergic afferents came from the ventro-lateral medulla (Al group), and only a few from the locus coeruleus complex (A6/A7 groups). A few dopaminergic neurons retrogradely labeled with flurogold were observed in the periventricular area of the hypothalamus. Rare serotoninergic fluorogold labeled neurons belonged to the dorsal raphe nucleus. Most of these afferents came from both sides of the brain, except for hypothalamic supraoptic and paraventricular nuclei. In the light of these anatomical data, we compared our results with data obtained from rats, and we discussed the putative role of these afferents in sheep in the regulation of several specific functions in which the retrochiasmatic area may be involved, such as reproduction.

Afferent Pathways↗
PubMed1998

Blockade of tyrosine hydroxylase activity in the median eminence partially reverses the long day-induced inhibition of pulsatile LH secretion in the ewe.

The photoperiod-induced stimulation of LH secretion is associated with a decrease in dopamine content, as well as in the activity of its rate limiting enzyme, tyrosine hydroxylase (TH), in the median eminence (ME) of the ewe. We therefore hypothesize that ME-TH activity can constitute a limiting factor of photoperiod-induced inhibition of LH pulsatile secretion. To test this hypothesis, we studied whether the inhibition of ME-TH activity can reverse the long day-induced inhibition of LH. Using microdialysis, a 3 mM solution of alpha methyl-p-tyrosine (alpha MPT; a competitive inhibitor of TH), was administered in the ME of ovariectomized ewes bearing a 0.5 cm oestradiol implant at the beginning of a LD-induced inhibition of LH secretion. The vehicle solution was infused for 4 h followed by a 3 mM alpha MPT solution infused for an additional 4 h. LH pulsatile secretory patterns within the same animal were compared between the control period and the alpha MPT period. alpha MPT infusion in the ME was associated with an increase in LH pulse frequency whereas it did not affect prolactin secretion. In conclusion, our results suggest that the inhibition of TH activity in the ME causes a stimulation of LH secretion in long-day inhibited ewes.

Animals↗
PubMed1997

Control of the circannual rhythm of reproduction by melatonin in the ewe.

Annual variations in day length are responsible for seasonal changes in reproductive activity in sheep. However, in constant photoperiodic conditions, ewes express an endogenous rhythm characterized by alternations of reproductive activity and quiescence that are not synchronized among animals. Thus, the main role of photoperiod in the natural environment appears to be the synchronization of this endogenous rhythm. Photoperiodic information is processed through a complex nervous and endocrine pathway to modulate reproductive activity. Light information perceived at the level of the retina is transformed through neural processing into an endocrine signal by the pineal gland: the nocturnal increase in melatonin release. Recent studies strongly suggest that melatonin has a hypothalamic target to modulate the reproductive neuroendocrine axis. Most LHRH perikarya are located in the preoptic area, but this region is devoid of melatonin receptors, and microimplants of melatonin placed in the preoptic area do not effect LHRH release. Thus, melatonin influences LHRH neurones indirectly and must involve interneurons. Good evidence now exists to demonstrate that a population of dopaminergic neurons with axons projecting to the median eminence is one of these interneurons.

Animals↗
PubMed1997

Estradiol acts locally within the retrochiasmatic area to inhibit pulsatile luteinizing-hormone release in the female sheep during anestrus.

In the present study we have identified a site of action of estradiol in the inhibition of LH secretion during anestrus in the ewe. In the first experiment, we studied six sites: the medial preoptic area, the lateral preoptic area, the ventromedial hypothalamus, the ventrolateral hypothalamus, the retrochiasmatic area (RCh), and the periventricular posterior hypothalamus. We compared the changes in parameters of pulsatile LH secretion (interpulse interval, mean nadir, mean amplitude, and mean area under curve) during three 6-h sampling periods: before and 30-36 h and 9 days after intracerebral implantation of crystalline estradiol. Animals that received estradiol in the RCh (n = 5) showed a significantly greater increase in both the intervals between pulses of LH (up 116%, p < 0.03) and the area under the curve (up 180%, p < 0.01) than any of the other groups of 7 animals. In the second experiment, implantation of estradiol in the RCh (n = 6) induced an increase in the intervals between pulses of LH (p < 0.03), whereas receiving an empty implant (n = 6) had no effect, showing that estradiol specifically induced increases in the intervals between pulses. Thus, estradiol appears to act in the RCh where the dopaminergic A15 nucleus, known to inhibit pulsatile LH release, is located.

Anestrus↗
PubMed1997

Characterization of the short day-induced decrease in median eminence tyrosine hydroxylase activity in the ewe: temporal relationship to the changes in luteinizing hormone and prolactin secretion and short day-like effect of melatonin.

In the ewe, photoperiod modulates LH and PRL secretion as well as median eminence (ME) dopaminergic activity. The studies reported here were designed to characterize the functional significance of this photoperiodic modulation of ME dopaminergic neuron activity in relation to the regulation of LH and PRL secretion. The aim of the first experiment was to assess whether photoperiodic changes in hypothalamic dopaminergic activity were temporally linked to changes in either PRL or LH secretion. The purpose of the second experiment was to determine whether melatonin mimicked the effects of photoperiod on ME dopaminergic activity. In the first experiment, LH and PRL secretion, hypothalamic tyrosine hydroxylase (TH) activity, and catecholamine contents were determined in ovariectomized estradiol-treated ewes either during long days (LD; control group) or after 5, 25, and 76 short days (SD). SD were associated with a stimulation of LH secretion and a decrease in ME TH activity, which were both expressed only in the 76 SD group. In contrast, the SD-induced inhibition of PRL secretion was already maximal in the 25 SD group. In the second experiment, LH secretion and hypothalamic dopaminergic activity were studied in ovariectomized estradiol-treated ewes kept in LD and then treated for 0 (control), 25, or 77 days with melatonin implants producing a SD-like effect on LH secretion. Melatonin induced a decrease in PRL secretion (observed after 25 days of treatment), as well as a stimulation of LH secretion and a decrease in ME TH activity and dopamine content (observed only after 77 days of treatment). In conclusion, the decrease in ME dopaminergic activity associated with SD exposure or the SD-like effect of melatonin appears unrelated to the regulation of PRL secretion. The SD-like effect of melatonin on ME dopaminergic activity suggests that melatonin mediates the effect of SD on this activity. The regulation of ME dopaminergic activity can thus be considered a probable step in the photoperiodic regulation of LH secretion.

Animals↗
PubMed1996

Photoperiodic modulation of monoamines and amino-acids involved in the control of prolactin and LH secretion in the ewe: evidence for a regulation of tyrosine hydroxylase activity.

Several neurotransmitters are implicated in the photoperiodic regulation of prolactin and luteinising hormone (LH) secretion in the ewe. This work investigated whether catecholamines, gamma-amino butyric acid (GABA), excitatory amino acids and serotonin diencephalic contents are affected by photoperiod and how such changes relate to the seasonal effects of photoperiod on LH and prolactin secretions. Moreover, to determine whether photoperiod can influence catecholamine biosynthesis, the activity of its rate limiting enzyme, tyrosine hydroxylase (TH) was also investigated. TH activity and the tissue content of the monoamines and their metabolites were measured in stalk-median eminence (SME), preoptic area (POA) and the mediobasal, mediodorsal and laterobasal aspects of the hypothalamus. Investigation of excitatory amino acids and GABA was limited to the POA and the SME. Ovariectomized ewes were initially maintained in long days (LD) for 70 days. Thereafter half the ewes remained exposed to long days and the other half were transferred onto short days (SD) for 63 to 66 days to induce a stimulation of LH secretion and an inhibition of prolactin secretion. In each photoperiodic regime, half the ewes were treated with a subcutaneous oestradiol implant (+E) and half were not (-E). As expected, short days induced a decrease in prolactin and an increase in pulsatile LH secretion. These neuroendocrine changes were associated with a decrease in the TH activity of the SME in both oestradiol treated and non treated animals (146.5 +/- 24.1, 167.6 +/- 26.5 U TH/g of tissue in LD-E and LD+E vs 83.5 +/- 12.4 and 95.0 +/- 30.2 U TH/g of tissue in SD-E and SD+E animals; P < or = 0.01). A similar and parallel short day-induced decrease was observed in the tissue content of dopamine and its metabolite, 3,4-dihydroxy-phenylacetic acid (SD level were 55% of LD levels, P < 0.05). In POA, a short day-induced decrease in dopamine (18%; P < or = 0.05) and GABA (16.4%; P < or = 0.05) content and an oestradiol-induced decrease in aspartate (15.6%; P < or = 0.05) content were found. This study provides the first report of a photoperiodic control of the synthesis activity of catecholaminergic neurones of the SME in the ewe. The photoperiod-induced changes in dopaminergic activity at the level of the SME were associated with changes in LH and prolactin secretion indicating that TH activity of dopaminergic neurones of the SME could be a critical component of the photoperiodic regulation of LH and/or prolactin secretion. In particular, this finding is in agreement with the hypothesis that photoperiod can control a dopaminergic pathway inhibitory of LH secretion and which ends in the median eminence.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Initiation of the oestradiol-induced inhibition of pulsatile LH secretion in ewes under long days: comparison of peripheral versus central treatment and neurochemical correlates.

In the ewe, the inhibition of pulsatile LH secretion by oestradiol during long days depends on dopaminergic activity and could involve amino acid transmitters. In the first experiment of the present study we observed the changes in LH secretion in ovariectomised ewes under long days immediately after subcutaneous implantation of oestradiol (peripheral treatment). In the second experiment, in order to identify the site of action of oestradiol, we observed the LH changes following intracerebral infusion of oestradiol through a microdialysis membrane (central treatment) within the preoptic area, the mediobasal hypothalamus (MBH) or the retrochiasmatic area (RCh) and measured amino acids and catecholaminergic transmitters and metabolites within the dialysates. With peripheral treatment, the amplitude, the nadir and the area under the LH pulse curve decreased within 4 to 8 h of the insertion of a subcutaneous oestradiol implant. After 18 h, the amplitude and the area under the pulses increased, as well as the intervals between pulses (from 49.9 + 1.4 min to 75.6 +/- 5.9 min). With central oestradiol treatment. LH changes were similar whatever the site of oestradiol infusion, suggesting either multiple sites of action or diffusion between structures. Twenty hours after the beginning of intracerebral oestradiol treatment, the amplitude and the area under the pulses increased, as did the interval between LH pulses (from 49.5 +/- 4.1 min to 73.2 +/- 14.2 min). Comparison of peripheral with central oestradiol treatment suggested that the long-lasting decrease in the nadir, as well as the transitory decrease in the amplitude and area, before 18 h in experiment 1 are reflections of hypophysial effects. In contrast, the increases in amplitude and area under the LH pulse curve seen 18-20 h after oestradiol in the two experiments could be due to the higher amplitude of LHRH pulses, as a result of an early stimulatory effect of oestradiol. After central oestradiol infusion, there was a decline in the concentration in the dialysate of two metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the RCh, suggesting an early inhibition of monoamine oxidase by the steroid. During the inhibition of LH pulsatility the concentration of gamma-aminobutyric acid in the dialysate from the RCh and the MBH increased, suggesting the participation of this transmitter in the changes induced by oestradiol under long days.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Effect of hypothalamic infusion of a dopamine D1 receptor antagonist on prolactin secretion in the ewe.

In this study we investigated whether dopamine D1 receptors in the hypothalamus are involved in the control of prolactin secretion in ovariectomised, oestradiol implanted ewes. The D1 antagonist SCH23390 or vehicle was infused into either the preoptic area (POA) or the ventromedial hypothalamus (VMH). During infusion into the VMH, prolactin concentrations declined significantly and did not return to control values until more than 60 min after the infusions had stopped. In contrast, infusion into the POA had no significant effect. These results are in accord with the hypothesis that dopaminergic pathways within the hypothalamus stimulate prolactin secretion via dopamine D1 receptors in the VMH.

Animals↗
PubMed1995

Efferent projections from the retrochiasmatic area to the median eminence and to the pars nervosa of the hypophysis with special reference to the A15 dopaminergic cell group in the sheep.

Anterograde tracers, viz. Phaseolus vulgaris leucoagglutinin and fluorescein dextran, were used in conjunction with tyrosine hydroxylase immunohistochemistry to study the projections of the A15 dopaminergic cell group towards the median eminence and pituitary in sheep. After injection of the tracers in the retrochiasmatic area, which contains the cell group A15, fibres containing anterograde tracer were observed in the internal zone of the median eminence and in the pars nervosa of the pituitary. Numerous tyrosine hydroxylase immunoreactive fibres were present in the external zone of the median eminence and in the pars intermedia and the pars nervosa of the pituitary, with characteristic patterns of organisation in each area. Most tyrosine hydroxylase-immunoreactive fibres containing fluorescein dextran were located in the pars nervosa, whereas only a few were observed in the internal zone of the median eminence. It was concluded that at least part of the dopaminergic innervation of the pars nervosa originated from the A15 group. These results provide morphological evidence for (1) the role of dopaminergic neurons of the A15 cell group in the seasonal control of prolactin secretion via the release of dopamine in the pars nervosa, and (2) putative physiological interactions between dopamine and the secretion of neurohypophysial hormones in sheep.

Animals↗
PubMed1995

Dopaminergic control of LH secretion by the A15 nucleus in anoestrous ewes.

Annual variations in the secretion of LH are responsible for seasonal changes in ovulatory activity in ewes. This hormonal pattern reflects an increase in the intensity of the negative feedback exerted by oestradiol under long days. Neuropharmacological studies have shown that this inhibition of LH secretion involves activation of catecholaminergic systems from preoptic and mediobasal hypothalamus (MBH) by oestradiol during anoestrus, and that 5-hydroxytryptamine inputs may also play a role. Within the MBH, the most important structures appear to be the retrochiasmatic region of the hypothalamus, which contains the A15 dopaminergic nucleus, and the median eminence, which contains the axon terminals of the GnRH cells controlling the pulsatile release of LH. In ovariectomized ewes in which oestradiol tonically inhibits LH secretion during the anoestrous season, LH pulse frequency is increased when the cells of the A15 nucleus are destroyed. The median eminence and other mediobasal structures contain more catecholamines and their metabolites under long days than under short days. Microdialysis of the A15 nucleus in vivo during long days revealed increased catecholaminergic activity under oestradiol treatment due to stimulation of tyrosine hydroxylase, the rate-limiting enzyme in the pathway of catecholaminergic synthesis. Tyrosine hydroxylase activity within the median eminence is increased under the various photoperiodic regimens that inhibit LH secretion. Neurochemical changes in the A15 nucleus and median eminence, in response to photoperiodic or oestradiol treatments, suggest a functional relationship which acts at the level of the GnRH axon terminals.

Anestrus↗
PubMed1994

Estradiol increases tyrosine hydroxylase activity of the A15 nucleus dopaminergic neurons during long days in the ewe.

In the ewe, the inhibition of LH secretion during long days results from increased negative feedback by estradiol. This effect depends on aminergic systems, mainly in the lateral retrochiasmatic area, a region that includes the dopaminergic A15 nucleus. Recently we demonstrated that the inhibition of LH secretion by estradiol under long days is accompanied by an increase in extracellular levels of amine metabolites (3,4-dihydroxyphenylacetic acid [DOPAC], homovanillic acid [HVA], and 5-hydroxyindolacetic acid [5-HIAA]) in the lateral retrochiasmatic area of the hypothalamus. The increase in catecholamine metabolite levels could be due to stimulation of tyrosine hydroxylase (TH) activity in the catecholaminergic systems of this region. In the present study, we tested this hypothesis by incorporating in vivo measurement of TH activity in the brain into our microdialysis model. We used this approach to first examine the effect of estradiol on TH activity in both the lateral retrochiasmatic area and the caudate nucleus during long days (experiment 1). Two dialysis sessions were carried out on each of six ewes: one after a 10-day estradiol treatment (s.c. implant) and the other after 10 days without estradiol treatment. Estradiol treatment reduced pulsatile LH secretion without affecting the secretion of prolactin. The steroid also significantly increased TH activity in the lateral retrochiasmatic area as assessed by the formation of L-3-4 dihydroxyphenylalanine (L-DOPA). There was no variation in the TH activity of the catecholaminergic systems of the caudate nucleus, suggesting that the effect of estradiol is specifically hypothalamic. In experiment 2, we estimated the relative contribution to the accumulation of L-DOPA in the lateral retrochiasmatic area by dopamine (DA) synthesis in the dopaminergic neurons and noradrenaline (NA) synthesis in the noradrenergic afferents of the A15 nucleus. This study also allowed us to test whether DOPAC and HVA molecules released in this medium originate from DA metabolism in dopaminergic cells of the A15 nucleus or in its noradrenergic afferents. We monitored TH activity as well as amine metabolite concentrations in the lateral retrochiasmatic area after a partial destruction of noradrenergic nerves in the brain using intracerebroventricular (i.c.v.) injections of nomifensine followed by 6-hydroxydopamine (6-OHDA) injections. We compared the responses in four experimental ewes with those in four control ewes receiving a single i.c.v. injection of nomifensine only. Decreases in extracellular concentrations of 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG) in the left lateral retrochiasmatic area and the tissue content of NA in the contralateral structure confirmed the effectiveness of the lesion of the noradrenergic endings.(ABSTRACT TRUNCATED AT 400 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Evidence that melatonin binding sites in the pars tuberalis do not mediate the photoperiodic actions of melatonin on LH and prolactin secretion in ewes.

An experiment was designed to determine whether the pars tuberalis is the site of action of melatonin involved in the photoperiodic control of LH and prolactin secretion in sheep. In an attempt to produce a 'short-day' effect on these hormones (i.e. stimulation of LH secretion and inhibition of prolactin release), microimplants of melatonin were placed either around the pituitary stalk (n = 6) or in the third ventricle (n = 5) as a control for the efficacy of the microimplant. Two sham-operated groups were treated with empty microimplants around the pituitary stalk (n = 4) or in the third ventricle (n = 3). A further two control groups were given either no melatonin (n = 5) or a melatonin implant s.c. (n = 6). Administration of a melatonin implant s.c. is known to stimulate LH secretion and inhibit prolactin release in photoperiodically inhibited ewes. During the experiment (over 75 days), there was no significant increase in LH concentrations for the ewes receiving melatonin around the pituitary stalk. A similar lack of response was noted in the untreated or sham-treated ewes. In contrast, LH concentrations increased in ewes treated with the melatonin microimplant in the third ventricle on day 37 (+/- 4) and remained high until day 62 (+/- 4). Similarly, in the ewes given an implant s.c., LH concentrations rose on day 39 (+/- 4) and remained high until the end of the study. Furthermore, melatonin caused an inhibition of prolactin secretion relative to controls only when delivered to these sites (i.e. s.c. and into the third ventricle, but not around the pituitary stalk).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Oestradiol increases the extracellular levels of amine metabolites in the ewe hypothalamus during anoestrus: a microdialysis study.

Giving a subcutaneous oestradiol implant during anoestrus to ovariectomized ewes inhibits pulsatile LH secretion. This effect results from an increased negative feedback of oestradiol and depends on the synthesis of biogenic amines, mainly from the mediobasal hypothalamus. In the present study, we examined the effect of oestradiol on the extracellular levels of amines and their metabolites. Eight ewes were sampled by microdialysis from the lateral retrochiasmatic area, including the dopaminergic A15 nucleus, during inhibition of LH secretion by long days. Two dialysis sessions were carried out on each ewe; one after a 10-day oestradiol treatment and the other one after 10 days without oestradiol treatment. Half of the ewes were first oestradiol-treated then untreated, the other half received the treatment in the reverse order. Oestradiol caused a decline in pulsatile LH secretion without affecting the secretion of prolactin. This steroid also led to a significant increase in the levels of amine metabolites: 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindoleacetic acid in the extracellular medium. These results demonstrate the effect of oestradiol on aminergic activity as related to changes in hormonal secretions during long days (16 h of light per 24 h). Thus our data support the hypothesis that amines inhibit gonadotrophic secretion during anoestrus in the ewe and suggest that there is an activation of the aminergic neurones from the retrochiasmatic area in this regulatory mechanism.

Anestrus↗
PubMed1991

Neurophysiological control of the secretion of gonadotrophin-releasing hormone and luteinizing hormone in the sheep--a review.

The anterior pituitary gland secretes pulses of luteinizing hormone (LH) in response to pulses of gonadotrophin-releasing hormone (GnRH) released into the hypophysial portal blood by the hypothalamus. The pulsatile nature of the secretions is very important because the frequency of the pulses is directly related to the activity of the GnRH neurons. We can therefore take advantage of this phenomenon to develop mechanistic interpretations of responses to experimental treatments designed to unravel the neural pathways that influence what is, arguably, the most important individual signal controlling the activity of the reproductive system. We might also resolve the disagreements in the literature covering the neuropharmacology of gonadotrophin secretion. In this review, we describe work towards this end in the sheep. Most (95%) of the 2500 GnRH cell bodies in the sheep brain are located in a region covering the anterior hypothalamus, the medial preoptic area, the diagonal band of Broca, and the septum. The axons of up to 50% of these cells terminate in the organum vasculosum of the lamina terminalis. The remainder terminate in the median eminence and form the final common pathway for the many factors that affect gonadotrophin secretion. Among the factors known to affect the frequency of the pulses (or the activity of the GnRH neurons) are nutrition, pheromones, photoperiod and gonadal steroids (negative and positive feedback). Factors that affect GnRH pulse amplitude are more difficult to determine because variations in pituitary responsiveness prevent the use of LH patterns as a 'bioassay'. Techniques developed recently have allowed the direct measurement of GnRH pulse amplitude and revealed inhibitory effects of oestradiol, but we do not know whether this effect is due to a reduction in the amount of GnRH released by each neurone or a reduction in the number of neurones releasing a pulse. It is unlikely that the factors that alter pulse frequency do so by directly affecting the GnRH cells. For example, it is obvious that other cells, with specific receptors for pheromonal or nutritional stimuli, formulate a signal that is transferred to the GnRH cells via interneurones. Similarly, it is likely that a hypothalamic clock intervenes between photoperiodic inputs and GnRH output. Opioidergic neurons have been proposed as a link in this system, but the complexity of their action makes it unlikely that they directly affect the GnRH neurons. The responses to steroids are simple and rapid, but steroid receptors have not been found in GnRH cells, so at least one other set of interneurones is involved.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗