Deciphering the Contributions of CRH Receptors in the Brain and Pituitary to Stress-Induced Inhibition of the Reproductive Axis

Raftogianni, Androniki; Roth, Lena C.; García‐González, Diego; Bus, Thorsten; Kühne, Claudia; Monyer, Hannah; Spergel, Daniel J.; Deussing, Jan M.; Grinevich, Valery

doi:10.3389/fnmol.2018.00305

Cited by 26 publications

(20 citation statements)

References 110 publications

(137 reference statements)

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“…The mechanisms through which stress impact upon the hypothalamic‐pituitary‐gonadal axis are not well established, although they are very likely to be multi‐factorial involving dependent and independent control by CRH neurones, 66,67 circulating corticosteroids 68 and direct neural (eg, brainstem) pathways 69 . Because the ARC kisspeptin neurones represent the GnRH pulse generator, 70 it is likely that different stressors impact upon these cells.…”

Section: Discussionmentioning

confidence: 99%

Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice

Nair

Aung

Porteous

et al. 2021

J Neuroendocrinology

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Chronic stress exerts multiple negative effects on the physiology and health of an individual. In the present study, we examined hypothalamic, pituitary and endocrine responses to 14 days of chronic variable stress (CVS) in male and female C57BL/6J mice. In both sexes, CVS induced a significant decrease in body weight and enhanced the acute corticosterone stress response, which was accompanied by a reduction in thymus weight only in females. However, single-point blood measurements of basal prolactin, thyroid-stimulating hormone, luteinising hormone, growth hormone and corticosterone levels taken at the end of the CVS were not different from those of controls. Similarly, pituitary mRNA expression of Fshb, Lhb, Prl and Gh was unchanged by CVS, although Pomc and Tsh were significantly elevated. Within the adrenal medulla, mRNA for Th, Vip and Gal were elevated following CVS. Avp transcript levels within the paraventricular nucleus of the hypothalamus were increased by CVS; however, levels of Gnrh1, Crh, Oxt, Sst, Trh, Ghrh, Th and Kiss1 remained unchanged.Oestrous cycles were lengthened slightly by CVS and ovarian histology revealed a reduction in the number of preovulatory follicles and corpora lutea. Taken together, these observations indicate that 14 days of CVS induces an up-regulation of the neuroendocrine stress axis and creates a mild disruption of female reproductive function. However, the lack of changes in other neuroendocrine axes controlling anterior and posterior pituitary secretion suggest that most neuroendocrine axes are relatively resilient to CVS.

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Section: Discussionmentioning

confidence: 99%

Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice

Nair

Aung

Porteous

et al. 2021

J Neuroendocrinology

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“…Research is also needed to determine which presynaptic neurons and glial cells release which transmitters onto GnRH neurons, and under which physiological conditions, as well as the roles of selected transmitter receptors of interest in GnRH neurons on GnRH neuron activity, GnRH/LH secretion, and fertility. Approaches such as rabies viral monosynaptic tracing [to identify the cells that make direct synaptic connections onto GnRH neurons (133)] and inducible GnRH neuron-specific deletion of selected transmitter receptor subunits [to avoid developmental compensation by other subunits or transmitters (134)], should help in this regard. In vivo or ex vivo recording, imaging, or photometry of GnRH neuron electrical activity or Ca 2+ dynamics (5, 19, 25, 135), in combination with optogenetic or chemogenetic stimulation or inhibition of presynaptic cells [to evoke or inhibit the release of transmitters from presynaptic cells (4, 26, 135–138)], along with new or improved methods for measuring GnRH/LH secretion, and monitoring of fertility (22, 137, 139, 140), should also help.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Gonadotropin-Releasing Hormone Neuron Activity and Secretion in Mice by Non-peptide Neurotransmitters, Gasotransmitters, and Gliotransmitters

Spergel

2019

Front. Endocrinol.

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Gonadotropin-releasing hormone (GnRH) neuron activity and GnRH secretion are essential for fertility in mammals. Here, I review findings from mouse studies on the direct modulation of GnRH neuron activity and GnRH secretion by non-peptide neurotransmitters (GABA, glutamate, dopamine, serotonin, norepinephrine, epinephrine, histamine, ATP, adenosine, and acetylcholine), gasotransmitters (nitric oxide and carbon monoxide), and gliotransmitters (prostaglandin E2 and possibly GABA, glutamate, and ATP). These neurotransmitters, gasotransmitters, and gliotransmitters have been shown to directly modulate activity and/or GnRH secretion in GnRH neurons in vivo or ex vivo (brain slices), from postnatal through adult mice, or in embryonic or immortalized mouse GnRH neurons. However, except for GABA, nitric oxide, and prostaglandin E2, which appear to be essential for normal GnRH neuron activity, GnRH secretion, and fertility in males and/or females, the biological significance of their direct modulation of GnRH neuron activity and/or GnRH secretion in the central regulation of reproduction remains largely unknown and requires further exploration.

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“…It is evident that stress-induced glucocorticoids inhibit the action of gonadotropin-releasing hormone (GnRH) neurons, gonadotrophs, and the gonads (Figure 1) [21]. Additionally, excessive CRH levels in depression lead to inhibition of the hypothalamic-pituitary-gonadal (HPG) axis [22][23][24].…”

Section: Depression and Its Effect On Hormonesmentioning

confidence: 99%

Depression and Its Effect on the Menstrual Cycle

Padda¹,

Khalid²,

Hitawala³

et al. 2021

Cureus

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A strong association is noted between depression and early perimenopause as well as menopause. The association was found to be the greatest in women with natural menopause at the age less than 40 years. Excessive corticotropin-releasing hormone (CRH) levels in depression lead to inhibition of the hypothalamic-pituitary-gonadal (HPG) axis and increased cortisol levels which further inhibits the action of gonadotropin-releasing hormone (GnRH) neurons, gonadotrophs, and gonads. The resulting changes in luteinizing hormone (LH) amplitude, follicle-stimulating hormone (FSH) levels, and LH pulse frequency were noted in patients with depression.Besides depression, earlier surgical menopause is associated with cognitive decline. In addition, it is seen that menopausal changes predisposed females to an increased risk of depression. The association between dysmenorrhea and depression was found to be bidirectional and congruent in most studies. Patients with dysmenorrhea and coexisting depression had enhanced pain perception along with a poor response to pain relief measures. Even the treatment of underlying depression has been shown to cause menorrhagia. On the other hand, amenorrhea has also been reported as a side effect of sertraline and electroconvulsive therapy. Menstrual disorders contribute to a significant number of outpatient gynecological visits per year in the United States. Co-existing or history of depression can either be the cause of or interfere in the treatment of these disorders. Furthermore, the treatment of depression can be the etiology of various menstrual abnormalities, while menstrual disorders themselves could be the cause of depression. The increasing prevalence of depression, women's health, multiple female-specific subtypes, and the preexisting burden of menstrual disorders necessitates more detailed studies on the effects of depression on the menstrual cycle.

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Deciphering the Contributions of CRH Receptors in the Brain and Pituitary to Stress-Induced Inhibition of the Reproductive Axis

Cited by 26 publications

References 110 publications

Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice

Impact of chronic variable stress on neuroendocrine hypothalamus and pituitary in male and female C57BL/6J mice

Modulation of Gonadotropin-Releasing Hormone Neuron Activity and Secretion in Mice by Non-peptide Neurotransmitters, Gasotransmitters, and Gliotransmitters

Depression and Its Effect on the Menstrual Cycle

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