A Role For Hypothalamic Catecholamines in the Regulation of Gonadotropin Secretion

doi:10.1016/B978-0-12-571140-1.50016-5

Proceedings of the 1983 Laurentian Hormone Conference

Volume 40 in Recent Progress in Hormone Research

1984, Pages 487-529

Proceedings of the 1983 Laurentian Hormone Conference

https://doi.org/10.1016/B978-0-12-571140-1.50016-5 Get rights and content

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This chapter discusses the role of the hypothalamic catecholaminergic system in regulating Luteinizing-hormone-releasing hormone (LHRH) secretion. The functional activity of the LHRH neuron can be affected by numerous putative neurotransmitters that stimulate or inhibit LHRH release. Some neurotransmitters may also activate or inhibit other primary inputs to affect the activity of the LHRH neuron. Coupled with these complex controls are modulatory influences exerted within the brain by changing serum levels of sex steroids on input circuitry, on genomic functions, and on ionic transport properties of the LHRH neuronal membrane. The entire sequence of neuroendocrine events that ultimately leads to ovulation depends on the maturation of ovarian follicles which, under the influence of basal concentrations of LH and follicle-stimulating hormone FSH, increase their secretion of estrogen into blood during the second day of diestrous and morning of proestrous. Estrogen may not only increase the releasable pool size of median eminence but it also is essential for the increased release of norepinephrine during the early afternoon of proestrus.

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Cited by (97)

Estradiol-17β-responsive A1 and A2 noradrenergic cells of the brain stem project to the bed nucleus of the stria terminalis in the ewe brain: A possible route for regulation of gonadotropin releasing hormone cells
2010, Neuroscience
We have studied brain stem cells in the ewe brain that project to the bed nucleus of the stria terminalis (BNST) and determined if these cells are activated by estradiol-17β. This would predicate an indirect role in the estradiol-17β regulation of gonadotropin releasing hormone (GnRH) cells, since these receive input from the BNST. Ovariectomized ewes received 50 μg estradiol-17β benzoate (i.m.) 1 h prior to brain collection, so that activated cells could be identified by Fos immunohistochemistry. Retrograde tracer (FluoroGold; FG), was injected into the three divisions of the BNST and labeled cells were mapped to the A1 and A2 regions and the parabrachial nucleus (PBN) of the brain stem. With FG injection into the dorsal and lateral BNST, all FG-containing cells in the caudal A1 and 45% of those in A2 stained for dopamine-β-hydroxylase (DBH), indicating noradrenergic type. No FG-labelled cells in the PBN were DBH-positive. In A1 and A2 respectively, 42% and 46% of FG-labelled cells were Fos-positive, with no double-labeling in cells of the PBN. In ewes receiving FG injections into the ventral BNST, estrogen receptor (ER)α-immunoreactive nuclei were found in 82% of A1-FG labeled and 38% of A2-FG labeled cells. No FG-labelled cells of the PBN were ERα-positive. Anterograde tracing from A1 with microruby injection identified projections to the PBN, BNST and preoptic area (POA). Thus, A1 and A2 noradrenergic neurons project to the BNST in the ewe brain, express ERα and are activated by estradiol-17β. These noradrenergic, estrogen-responsive cells may provide indirect input to GnRH cells, via the BNST.
The role of the brain in female reproductive aging
2009, Molecular and Cellular Endocrinology
In middle-aged women, follicular depletion is a critical factor mediating the menopausal transition; however, all levels of the hypothalamic–pituitary–gonadal (HPG) axis contribute to the age-related decline in reproductive function. To help elucidate the complex interactions between the ovary and brain during middle-age that lead to the onset of the menopause, we utilize animal models which share striking similarities in reproductive physiology. Our results show that during middle-age, prior to any overt irregularities in estrous cyclicity, the ability of 17β-estradiol (E₂) to modulate the cascade of neurochemical events required for preovulatory gonadotropin-releasing hormone (GnRH) release and a luteinizing hormone (LH) surge is diminished. Middle-aged female rats experience a delay in and an attenuation of LH release in response to E₂. Additionally, although we do not observe a decrease in GnRH neuron number until a very advanced age, E₂-mediated GnRH neuronal activation declines during the earliest stages of age-related reproductive decline. Numerous hypothalamic neuropeptides and neurochemical stimulatory inputs (i.e., glutamate, norepinephrine (NE), and vasoactive intestinal peptide (VIP)) that drive the E₂-mediated GnRH/LH surge appear to dampen with age or lack the precise temporal coordination required for a specific pattern of GnRH secretion, while inhibitory signals such as gamma-aminobutyric acid (GABA) and opioid peptides remain unchanged or elevated during the afternoon of proestrus. These changes, occurring at the level of the hypothalamus, lead to irregular estrous cycles and, ultimately, the cessation of reproductive function. Taken together, our studies indicate that the hypothalamus is an important contributor to age-related female reproductive decline.
The gonadotropin-releasing hormone and its receptor
2009, Hormones, Brain and Behavior Online
Gonadotropin-releasing hormone (GnRH) is the central neuropeptide in vertebrates that controls the synthesis and release of luteinizing hormone and follicle-stimulating hormone in the anterior pituitary. Its prevalence suggests that it is required for the reproductive success of many species. It is therefore important to understand the factors that control the synthesis and release of GnRH in the brain as well as the mechanisms by which GnRH controls the responses of its targets in the central nervous system and in the anterior pituitary. This chapter focuses on the development and anatomy of the GnRH neuronal system; some of the actions and mechanisms that regulate GnRH neurons; and the localization, regulation, and functional aspects of GnRH receptors in the brain. Finally, the mechanisms of action of GnRH in the anterior pituitary or pituitary-derived cell lines are discussed.
The role of noradrenaline in the generation of the preovulatory LH surge in the ewe
2006, Domestic Animal Endocrinology
Citation Excerpt :
Such systems include those that produce gamma-amino butyric acid (GABA) [25–27] and opioids [25]. Studies in rats indicate an important role for NA in the regulation of GnRH cells by ovarian steroids [28,29] and measurement of turnover rates of catecholamines in the hypothalamus indicate release of NA at the time of the preovulatory LH surge in rats [30–33]. In sheep, NA has been shown to regulate LH secretion when micro-injected into the POA [34].
Increasing plasma estrogen (E) levels during the follicular phase of the estrous cycle trigger the pre-ovulatory surge of gonadotropin-releasing hormone (GnRH)/LH. Noradrenaline (NA)-producing cells of the brain stem are involved in regulating GnRH cells and project to the preoptic area (POA) and bed nucleus of stria terminalis (BnST). Input to GnRH cells may be direct or indirect, via relay neurons in the POA/BnST. To investigate this, we ascertained whether an α₁-adrenergic antagonist would block/delay the LH surge in ovariectomised (OVX), E-treated ewes. E benzoate (EB) (50 μg) was injected (i.m.) and Doxazosin (100 nmol/h) or vehicle was infused into the third ventricle 2–26 h after EB injection. Doxazosin reduced the magnitude of the LH surge, but did not affect timing. To determine if NA is released in the POA/BnST of cyclic ewes, we immunostained dopamine-β-hydroxylase (DBH) in terminal fields. Reduced numbers of varicosities staining for DBH indicates release of NA. The number of varicosities immunostained for DBH was reduced in the dorsal and lateral BnST during the follicular phase and during the preovulatory LH surge compared to the luteal phase. These data suggest that noradrenergic mechanisms are involved in generation of the GnRH/LH surge via projections to the BnST and relay to GnRH cells. Since Doxasozin reduced the magnitude of the LH surge in the E-treated OVX ewe, and release of NA in cyclic ewes occurred during the follicular phase of the estrous cycle, we speculate that NA is a permissive factor in surge generation. Thus, increased noradrenergic activity is not a trigger mechanism for initiation of the surge.
Luteinizing hormone-releasing hormone (LHRH) neurons: Mechanism of pulsatile LHRH release
2001, Vitamins and Hormones
Many types of neurons and glia exhibit oscillatory changes in membrane potentials and cytoplasmic Ca²⁺ concentrations. In neurons and neuroendocrine cells an elevation of intracellular Ca²⁺ concentration is associated with neurosecretion. Since both oscillatory membrane potentials and intracellular Ca²⁺ oscillations have been described in primary LHRH neurons and in GT1 cells, it is evident that an endogenous pulse-generator/oscillator is present in the LHRH neuron in vitro. The hourly rhythms of LHRH neurosecretion appear to be the synchronization of a population of LHRH neurons. How a network of LHRH neurons synchronizes their activity, i.e., whether by the result of synaptic mechanisms or electrical coupling through gap junctions or through a diffusible substance(s), remains to be clarified. Even though LHRH neurons themselves possess an endogenous pulse-generating mechanism, they may be controlled by other neuronal and nonneuronal elements in vivo. NE, NPY, glutamate, and GABA are neurotransmitters possibly controlling pulsatile LHRH release, and NO, CAMP, and ATP may be diffusible substances involved in pulsatile LHRH release without synaptic input. Although synaptic inputs to the perikarya of LHRH neurons could control the activity of LHRH neurons, a line of evidence suggests that direct neuronal and nonneuronal inputs, especially those from astrocytes to LHRH neuroterminals, appear to be more important for pusatile LHRH release.
Cellular mechanism of pulsatile LHRH release
1998, General and Comparative Endocrinology
One of the most intriguing characteristics of the luteinizing hormone-releasing hormone (LHRH) neuronal system in mammalian species is the pulsatile release pattern of the peptide from the hypothalamus into the portal circulation, which is essential for the maintenance of normal reproductive function. In this review article the new concept that LHRH neurons possess an endogenous pulse-generating mechanism, but this is modified by other neuronal and nonneuronal inputs is discussed.

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