scholarly journals Anti-Müllerian Hormone, Growth Hormone, and Insulin-Like Growth Factor 1 Modulate the Migratory and Secretory Patterns of GnRH Neurons

2021 ◽  
Vol 22 (5) ◽  
pp. 2445
Author(s):  
Rossella Cannarella ◽  
Alyssa J.J. Paganoni ◽  
Stefania Cicolari ◽  
Roberto Oleari ◽  
Rosita A. Condorelli ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Cell Line ◽  
Hypogonadotropic Hypogonadism ◽  
Delayed Puberty ◽  
Insulin Like Growth Factor ◽  
Gnrh Neuron ◽  
Neuron Migration ◽  
Gnrh Secretion ◽  
Gnrh Neurons

Anti-Müllerian hormone (AMH) is secreted by Sertoli or granulosa cells. Recent evidence suggests that AMH may play a role in the pathogenesis of hypogonadotropic hypogonadism (HH) and that its serum levels could help to discriminate HH from delayed puberty. Moreover, the growth hormone (GH)/insulin-like growth factor 1 (IGF1) system may be involved in the function of gonadotropin-releasing hormone (GnRH) neurons, as delayed puberty is commonly found in patients with GH deficiency (GHD) or with Laron syndrome, a genetic form of GH resistance. The comprehension of the stimuli enhancing the migration and secretory activity of GnRH neurons might shed light on the causes of delay of puberty or HH. With these premises, we aimed to better clarify the role of the AMH, GH, and IGF1 on GnRH neuron migration and GnRH secretion, by taking advantage of previously established models of immature (GN11 cell line) and mature (GT1-7 cell line) GnRH neurons. Expression of Amhr, Ghr, and Igf1r genes was confirmed in both cell lines. Cells were then incubated with increasing concentrations of AMH (1.5–150 ng/mL), GH (3–1000 ng/mL), or IGF1 (1.5–150 ng/mL). All hormones were able to support GN11 cell chemomigration. AMH, GH, and IGF1 significantly stimulated GnRH secretion by GT1-7 cells after a 90-min incubation. To the best of our knowledge, this is the first study investigating the direct effects of GH and IGF1 in GnRH neuron migration and of GH in the GnRH secreting pattern. Taken together with previous basic and clinical studies, these findings may provide explanatory mechanisms for data, suggesting that AMH and the GH-IGF1 system play a role in HH or the onset of puberty.

scholarly journals Deletion of the Homeodomain Protein Six6 From GnRH Neurons Decreases GnRH Gene Expression, Resulting in Infertility

Endocrinology ◽  
2019 ◽  
Vol 160 (9) ◽  
pp. 2151-2164 ◽  
Author(s):  
Erica C Pandolfi ◽  
Karen J Tonsfeldt ◽  
Hanne M Hoffmann ◽  
Pamela L Mellon
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Neuronal Cell ◽  
Delayed Puberty ◽  
Homeodomain Protein ◽  
Gnrh Neuron ◽  
Direct Role ◽  
Hpg Axis ◽  
Gnrh Neurons

Abstract Hypothalamic GnRH (luteinizing hormone–releasing hormone) neurons are crucial for the hypothalamic-pituitary-gonadal (HPG) axis, which regulates mammalian fertility. Insufficient GnRH disrupts the HPG axis and is often associated with the genetic condition idiopathic hypogonadotropic hypogonadism (IHH). The homeodomain protein sine oculis–related homeobox 6 (Six6) is required for the development of GnRH neurons. Although it is known that Six6 is specifically expressed within a more mature GnRH neuronal cell line and that overexpression of Six6 induces GnRH transcription in these cells, the direct role of Six6 within the GnRH neuron in vivo is unknown. Here we find that global Six6 knockout (KO) embryos show apoptosis of GnRH neurons beginning at embryonic day 14.5 with 90% loss of GnRH neurons by postnatal day 1. We sought to determine whether the hypogonadism and infertility reported in the Six6KO mice are generated via actions within the GnRH neuron in vivo by creating a Six6-flox mouse and crossing it with the LHRHcre mouse. Loss of Six6 specifically within the GnRH neuron abolished GnRH expression in ∼0% of GnRH neurons. We further demonstrated that deletion of Six6 only within the GnRH neuron leads to infertility, hypogonadism, hypogonadotropism, and delayed puberty. We conclude that Six6 plays distinct roles in maintaining fertility in the GnRH neuron vs in the migratory environment of the GnRH neuron by maintaining expression of GnRH and survival of GnRH neurons, respectively. These results increase knowledge of the role of Six6 in the brain and may offer insight into the mechanism of IHH.

scholarly journals The Differential Roles for Neurodevelopmental and Neuroendocrine Genes in Shaping GnRH Neuron Physiology and Deficiency

2021 ◽  
Vol 22 (17) ◽  
pp. 9425
Author(s):  
Roberto Oleari ◽  
Valentina Massa ◽  
Anna Cariboni ◽  
Antonella Lettieri
Keyword(s):  
Phenotypic Variability ◽  
Hypogonadotropic Hypogonadism ◽  
Neuroendocrine Cells ◽  
Delayed Puberty ◽  
Neuronal System ◽  
Gnrh Neuron ◽  
Neuron Development ◽  
Gnrh Neurons ◽  
Genes Encoding ◽  
Functional Relevance

Gonadotropin releasing hormone (GnRH) neurons are hypothalamic neuroendocrine cells that control sexual reproduction. During embryonic development, GnRH neurons migrate from the nose to the hypothalamus, where they receive inputs from several afferent neurons, following the axonal scaffold patterned by nasal nerves. Each step of GnRH neuron development depends on the orchestrated action of several molecules exerting specific biological functions. Mutations in genes encoding for these essential molecules may cause Congenital Hypogonadotropic Hypogonadism (CHH), a rare disorder characterized by GnRH deficiency, delayed puberty and infertility. Depending on their action in the GnRH neuronal system, CHH causative genes can be divided into neurodevelopmental and neuroendocrine genes. The CHH genetic complexity, combined with multiple inheritance patterns, results in an extreme phenotypic variability of CHH patients. In this review, we aim at providing a comprehensive and updated description of the genes thus far associated with CHH, by dissecting their biological relevance in the GnRH system and their functional relevance underlying CHH pathogenesis.

Consensus on the change of criteria for cure of acromegaly during the last decade

2011 ◽  
Vol 152 (18) ◽  
pp. 703-708 ◽  
Author(s):  
Gábor László Kovács ◽  
Judit Dénes ◽  
Erika Hubina ◽  
László Kovács ◽  
Sándor Czirják ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Disease Control ◽  
Short Communication ◽  
Consensus Statement ◽  
Diagnosis And Treatment ◽  
Clinical Aspects ◽  
Insulin Like Growth Factor ◽  
Criteria For Diagnosis ◽  
Definition Of

The Acromegaly Consensus Group redefined the consensus criteria for cure of acromegaly. 74 neurosurgeons and experienced endocrinologists summarized the latest results on diagnosis and treatment of acromegaly. In this consensus statement the reliable growth hormone and insulin-like growth factor-1 assays were established. Definition of disease control was discussed based on the available publications and evidence. This short communication summarizes the clinical aspects of consensus criteria for diagnosis and cure of acromegaly based on the original article. Orv. Hetil., 2011, 152, 703–708.

Sign in / Sign up

Export Citation Format

Share Document