Role of medial preoptic GABA neurones in regulating luteinising hormone secretion in the ovariectomised rat

Herbison, Allan E.; Chapman, Chris; Dyer, R. G.

doi:10.1007/bf00231851

Cited by 70 publications

(45 citation statements)

References 29 publications

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“…Subsequent studies, however, have suggested that there may also be a nongenomic component to the action of P, possibly through P metabolites acting through the GABA A receptor (17). In rats, GABA has an inhibitory effect on GnRH (39) and LH secretion (40,41). GABA has also been implicated in LH inhibition in sheep (42) and specific manipulation of the GABA A , but not GABA B , receptor suppresses LH secretion (43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

Skinner

Evans

Delaleu

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

142

122

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Progesterone (P) powerfully inhibits gonadotropin-releasing hormone (GnRH) secretion in ewes, as in other species, but the neural mechanisms underlying this effect remain poorly understood. Using an estrogen (E)-free ovine model, we investigated the immediate GnRH and luteinizing hormone (LH) response to acute manipulations of circulating P concentrations and whether this response was mediated by the nuclear P receptor. Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0-12 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12-24 hr, P implant removed; 24-36 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3␣-hydroxy-5␣-pregnan-20-one, which operates through the type A ␥-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system. Progesterone (P) is the dominant ovarian steroid present in the peripheral circulation during the mammalian reproductive cycle and serves a number of important regulatory roles. The luteal phase elevation in P inhibits pulsatile gonadotropinreleasing hormone (GnRH) and luteinizing hormone (LH) secretion (1-4) and prevents the occurrence of GnRH (5) and LH (6, 7) surges in response to fluctuations in peripheral estrogen (E) levels that accompany the waves of follicular growth occurring in the ovary (8). We have also recently demonstrated that the luteal phase elevation of P affects both the timing of the LH surge relative to E stimulation and the magnitude of the coincident GnRH surge (D.C.S., N.P.E., and A.C., unpublished results). Despite its obvious importance in regulating reproduction, little is known about how and where P acts to powerfully inhibit the neuroendocrine reproductive axis.Our first study, using the hypophyseal portal cannulation approach, assessed directly the timing of the changes in GnRH secretion that follow both an abrupt decrease and an increase in circulating P concentrations. To avoid potential P-E interactions, short-term ovariectomized (OVX) ewes were used.Since P modulates tonic LH secretion by affecting GnRH pulse frequency (1-4), it is held that P acts through neural targets and putative candidates include the opioidergic, noradrenergic, and ␥-aminobutyric acid (GABA) systems (9, 10). The p...

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Section: Discussionmentioning

confidence: 99%

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

Skinner

Evans

Delaleu

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

142

122

View full text Add to dashboard Cite

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“…Our recent study showing that extracellular GABA concentrations in the supraoptic nucleus do not alter in response to suckling or individual milk ejections (Voisin, Chapman, Poulain & Herbison, 1994) suggests that the role of GABA may be permissive in nature and not involved directly in evoking each high frequency burst of firing. It is of interest to note that GABA has been hypothesized to play a very similar role to help generate pulsatile activity within the gonadotrophin-releasing hormone (GnRH) neurones; extracellular GABA concentrations do not change in relation to individual pulses of luteinizing hormone and both GABAA receptor agonists and antagonists infused into the immediate vicinity of the GnRH neurones inhibit pulsatile activity (Herbison, Chapman & Dyer, 1991). Together, these observations suggest that an on-going balance of GABA activity may be essential for the normal functioning of several neuroendocrine networks and we provide here such evidence for the magnocellular oxytocin neurones during lactation.…”

Section: Discussionmentioning

confidence: 99%

Central inhibitory effects of muscimol and bicuculline on the milk ejection reflex in the anaesthetized rat.

Voisin

Herbison

Poulain

1995

The Journal of Physiology

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1. In order to determine whether GABAergic mechanisms are involved in the control of the milk ejection reflex in the rat, we examined the effects of central administration of a GABAA receptor agonist (muscimol) and antagonist (bicuculline) on the milk ejection reflex in the urethane-anaesthetized rat. 2. Intracerebroventricular (i.c.v.) injection of both muscimol (n = 17), at doses of 5, 10 and 20 ng, and bicuculline (n = 15), at doses of 0 01, 0 1 and 0 3 ,g, inhibited the milk ejection reflex in a dose-dependent manner. The bicuculline-induced inhibition was accompanied by desynchronization of the electroencephalogram and, at the highest dose, by alteration in the sensitivity of the mammary gland to oxytocin. No significant effect on the milk ejection reflex was seen with i.c.v. isotonic saline (n = 5). 3. Injection of 20 (n = 5) or 40 ng (n = 2) muscimol or 0 1 ,ug bicuculline (n = 5) I.c.v. did not significantly alter the rise in intramammary pressure evoked by electrical stimulation of the neurohypophysis. 4. Bilateral 400 nl microinfusions directly into the supraoptic nuclei of either muscimol (20-100 ng ml-'; n = 10) or bicuculline (0'15 ng ml-'; n = 5) resulted in an inhibition of the milk ejection reflex, which was not accompanied by desynchronization of the electroencephalogram. 5. The effects of I.c.v. injections of muscimol (15 and 20 ng) and bicuculline (0 01, 0-12 and 0 3 ,g) on the electrical activity of twenty-seven antidromically identified supraoptic magnocellular neurones were examined. Both compounds resulted in an inhibition of the background firing of oxytocinergic and vasopressinergic cells, and delayed the occurrence of high frequency bursts in oxytocin neurones. In five supraoptic neurones, bicuculline induced a transient activation before inhibition. 6. The powerful inhibitory action on the milk ejection reflex of both muscimol and bicuculline provides evidence for the importance of GABA neurones in maintaining the functional integrity of the mechanisms which allow the intermittent and pulsatile release of oxytocin during suckling.

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“…Several lines of evidence indicate that in vivo the IAA y-aminobutyric acid (GABA) inhibits GnRH release by a mechanism residing in the POA, i.e. by an action at GnRH perikarya (Herbison et al 1991;Jarry et al 1991;Scott & Clarke, 1993). Pharmacological experiments with EAA agonists or antagonists prove the importance of EAA for both the regulation of pulsatile GnRH release and the induction of the pre-ovulatory LH surge (Lopez et al 1990;Ping et al 1994).…”

Section: MD Brown School Of Sport and Exercise Sciences University Omentioning

confidence: 99%

Symposium Proceedings

1995

The Journal of Physiology

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Starting with the earliest in vivo studies of the microcirculation, observers have been impressed with the variability and heterogeneity of microcirculation blood flow. The question I should like to address is how heterogeneity of microvascular perfusion influences transport of diffusible solutes, and how control of heterogeneity may contribute to regulation of blood-tissue exchange. Available exchange vessel surface area and inter-exchange vessel distances are controlled at the arteriolar level by the number of vessels open to the supply of arterial blood. When metabolic requirements are low, only a fraction of the exchange vessels in a vascular network are perfused; as metabolic activity increases, more exchange vessels are recruited. However, the efficiency with which available exchange vessel surface is utilized for diffusion of a given solute depends on the distribution of individual blood flow/permeability surface area ratios (Q/PS) in the network. Maximum efficiency (full utilization of available PS) is achieved when Q/PS is uniform.In vivo observations of red blood cell velocities show wide variation among individual exchange vessels of the same class (capillaries, postcapillary venules); presumably the same is true of plasma velocities. Flow velocity is only one of the factors that determines local transport; the critical parameter is the product of velocity and vessel radius divided by vessel length times solute permeability (v. r/ 1 P). The impression I get from published intra-vital microscope data is that this ratio may vary even more widely than velocity alone. Physiological measurements of solute transport in whole organs provide indirect support for broad heterogeneity of perfusion, at least in low metabolic states. In resting skeletal muscles the apparent (measured) PS products for 86Rb and 51Cr EDTA increase with increasing perfusion rate, approaching limiting values at high flow rates, as predicted for a heterogeneity perfused assemblage of exchange vessels. Estimated coefficients of variation (cv = S.D./mean) of Q/PS or v. r/ 1 P lie in the range 07-09.In heterogeneously perfused organs and tissues, the degree of heterogeneity (cv of Q/PS) and the total blood flow are potentially important secondary regulators of capillary transport, because they determine the efficiency with which the primary controlling factors, total blood flow and available exchange vessel surface area, are utilized (note that blood flow acts both directly and indirectly). Efficiency, defined as the ratio of apparent PS to the maximum PS at uniform perfusion, is inversely related to the degree of heterogeneity and directly related to the mean flow velocity. There is conflicting evidence in the literature concerning the degree to which alteration of Q/PS heterogeneity is involved in adaptive control of diffusion exchange. However, even with constant total PS and fixed heterogeneity, an increase in total blood flow can decrease the influence of heterogeneity on transport and thus contribute substantially to Berlin 33, Ger...

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Role of medial preoptic GABA neurones in regulating luteinising hormone secretion in the ovariectomised rat

Cited by 70 publications

References 29 publications

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor

Central inhibitory effects of muscimol and bicuculline on the milk ejection reflex in the anaesthetized rat.

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