Insight into the ontogeny of GnRH neurons from patients born without a nose

Autor: Rolando Prada, Tatiana Pineda Buitrago, Cristiano Tonello, Hallvard Reigstad, Rameshwar Prasad, Jennifer Henkind, Brooke Meader, Natalie D. Shaw, Susan Kim, Bianca E Russell, Janice Lee, John M. Graham, Gazal Arora, Kathleen A. Williamson, Nancy Mizue Kokitsu-Nakata, Ravikumar Balasubramanian, Rita Volochayev, Yline Capri, Stephanie B. Seminara, Kaoru Inoue, Jennifer R. Law, Germaine Y Noukelak, Orlando Perez, Andrew A. Dwyer, Laura J. Chalmers, Uttam Mondal, Angela Delaney, Konstantinia Almpani, Kathryn B Salnikov, Janet E. Hall, Roseli Maria Zechi-Ceide, Kosuke Morioka, Katharina Steindl, Chie-Hee Cho, Jose Elias Garcia, Gisele da Silva Dalben, Lacey Plummer, William F. Crowley, Christina Jacobsen, Michiyo Mizota, Angela E. Lin, Angela M. Kaindl, Anita Rauch, Nicole P DiOrio, Scott A. Clements, Siulan Vendramini-Pittoli
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Olfactory system
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Biochemistry
Cohort Studies
Gonadotropin-Releasing Hormone
Olfaction Disorders
0302 clinical medicine
Endocrinology
Medicine
Child
Neurons
GnRH Neuron
Clinical Research Article
Reproductive function
FENÓTIPOS
Olfactory Pathways
Organ Size
Middle Aged
Hypothalamus
Child
Preschool
Female
Luteinizing hormone
hormones
hormone substitutes
and hormone antagonists
Adult
endocrine system
medicine.medical_specialty
Adolescent
Neurogenesis
Context (language use)
Nose
Young Adult
03 medical and health sciences
Internal medicine
Humans
Abnormalities
Multiple
Gonads
Aged
Breast development
business.industry
Hypogonadism
Biochemistry (medical)
Infant
Luteinizing Hormone
030104 developmental biology
Follicle Stimulating Hormone
business
030217 neurology & neurosurgery
Hormone
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
J Clin Endocrinol Metab
Popis: Context The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed. Objective The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures. Methods We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients. Results All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient. Conclusions Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.
Databáze: OpenAIRE
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