Deciphering the Morphological Dilemma of Multiple Noses

Deciphering the Morphological Dilemma of Multiple Noses Dr. Atindra Datta, MBBS, MS  Retired Professor, R G Kar Medical College, Kolkata, India Dr. Anustup Datta, MD (Internal Medicine) Fellow in Nephrology S R, Department of Nephrology, Medical College, Kolkata, India Abstract Extra cranial origin of GnRH, a wonder neuron who sets up the Hypothalamus-Pituitary-Gonad (HPG) axis but also shape up the brain both structurally and functionally during mini-puberty. The establishment of HPG axis needs a population of around 2000 GnRH neurons but a surge of GnRH population occurs at Mini puberty to the tune of 8000 who go scattered throughout the brain to mature it up. However, prerequisite of GnRH formation required the nasal placode on face. So, a deficiency of GnRH population during Mini puberty makes another nasal protrusion on the face postnatally. Foreword This article is conceptualized after reading the review article “New Horizons: Gonadotrophin-releasing hormone and cognition” by Vincent Prevot, Manuel Tena Sempere and Nelle Pitte Loud [1]. Introduction GnRH neurons are not born in the brain. During development of face a frontonasal process descends from the scalp over forebrain and reaches face. On its lower margin laterally nasal (Olfactory) placodes develop who immediately invaginate inward to form nasal pits. This nasal placode is the site of formation of GnRH neurons. Right from all vertebrates to all mammals GnRH neurons are created in the nasal cavities and migrate along olfactory nerve terminals to forebrain and hypothalamus. During birth GnRH neurons have reached their final destination of hypothalamus by diffusely distributed and particularly abundant in the preoptic region in rodents and sheep and are found in the tuberal region of the hypothalamus close to the median eminence. In other species like primates and humans the axons of hypophysiotropic GnRH neurons target pericapillary space of the median eminence specifically to release neurohormone in the fenestrated vessels of the pituitary portal circulation. Around the peri gestational period about 2000 GnRH neurons reached the hypothalamic region to establish the HPG axis. This is the first job established for normal physiological work of GnRH for smooth function of hypothalamic releasing hormone to pituitary trophic hormone to gonadal LH and FSH hormones. Later 8000 immunoreactiveGnRH neurons are found scattered in the extra hypothalamic brain areas including neocortex but these neurons are not involved in the control of HPG axis. Ojeda and colleagues [7] explicitly studied the postnatal development of the GnRH neurons. In this, GnRH neurons, undergo sequential maturation events affecting biosynthesis capacity, morphology and neurosecretory pattern, ultimately leading to sexual maturation and pubertal initiation. The neonatal period comprising of first week of extra uterine life, postnatal day O or PO, then infantile period extending from P8 to weaning which is characterized by “mini-puberty” when a transient surge of GnRH production occurs, that leads to gonadal activation in humans [2-5] and the juvenile period, during which GnRH system progressively matures. Mini puberty driven by GnRH is a critical period for brain development armed with 8000 GnRH neurons. Preclinical studies have shown that during Mini puberty an infantile ‘critical period’ lasting just a few days in rodents and months in humans when a dramatic switch in micro-RNA expression pattern of GnRH neurons inverts the balance between inductive and repressive signals, triggering increased hypothalamic GnRH expression and controlling the crucial transition from More Information How to cite this article: Datta A, Datta A. Deciphering the Morphological Dilemma of Multiple Noses. Eur J Med Health Res, 2025;3(6):97-9. DOI: 10.59324/ejmhr.2025.3(6).15 Keywords: GnRH neurons, HPG axis, Mini puberty, Nasal Placode, Nitric Oxide, LH, FSH. This work is licensed under a Creative Commons Attribution 4.0 International License. The license permits unrestricted use, distribution, and reproduction in any medium, on the condition that users give exact credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if they made any changes. EUR J MED HEALTH RES Volume 3 | Number 6 | 2025 98 the early infantile phase at low level to the GnRH fueled run up to puberty. During Mini puberty, activation GnRH neurons induce a dramatic rise in FSH level, which promotes steroidogenesis at the gonads. This results in an increase in circulating gonadal steroids which feedback on to the brain where they activate neurons expressing their receptors and in particular to hypothalamic neurons producing Nitric Oxide (NO) that control both the amplitude and termination of Mini pubertal FSH surge. Failure of the infantile activation of NO synthesizing neurons in altered Mini puberty and reproductive, sensory and cognitive co-morbidities later in life that can be reversed by infantile exposure to inhaled NOcreated with BioRender.com. Figure 1: The Figure Shows a Bright and Intelligent Facies of a Child with Extra Nasal Aperture Indicating Extra Nose Produced 8000 new GnRH Neurons to Make the Child Smart, Bright and Beautiful Source: [6] Discussion The look of the children with extra nose is more bright and intelligent, compared with Down Syndrome. To start with babies born with single or double nose had deficiency of neurons and this neuronal status was assessed by, the then brain at Mini puberty. The GnRH population was 2000 and a surge of GnRH production is required to the tune of 8000 for the further development of brain. But explained previously this production cannot be performed anywhere in brain. It required again a nasal placode on face and production is performed in nasal cavity. As a sequela in postnatal time a nasal placode developed on face followed by invagination to nasal pit and eventually to full form of nose as like the trunk of an elephant by the side of an existing nose. However, this development did not ease respiration but to enable production of extra GnRH neurons. Conclusion While studying the facial anomalies it was discovered that some children have extra nose. On close observation, it was revealed that child was born with a single or double nasal aperture but in postnatal life a new nose originated. This anomaly was described by Datta A. [6]. Later he came across with a review article that described the wonders of GnRH which has a profound influence on establishment of HPG axis for smooth functioning of sex hormones. This work is performed by GnRH population of 2000. However, GnRH has another function of brain maturation which required GnRH population of 8000. If the baby is born with neural deficiency, then in the postnatal life another nose developed as a prerequisite to production of extra population of GnRH neurons. However, on observation, it poses a challenge to plastic surgeons to bring normalcy and beauty to facial configuration. Reference [1] Prévot V, Tena-Sempere M, Pitteloud N. New Horizons: Gonadotropin-Releasing Hormone and Cognition. J Clin Endocrinol Metab. 2023 Oct 18;108(11):2747-2758. doi:10.1210/clinem/dgad319. [2] Prevot V. Puberty in mice and rats. In: Plant TM, Zeleznik J, editors. Knobil and Neill’s Physiology of Reproduction. 4th ed. Elsevier; 2015. p. 1395-1439. [3] Kuiri-Hänninen T, Sankilampi U, Dunkel L. Activation of the hypothalamic-pituitary-gonadal axis in infancy: minipuberty. Horm Res Paediatr. 2014;82(2):73-80. doi:10.1159/000362414. [4] Terasawa E. The mechanism underlying the pubertal increase in pulsatile GnRH release in primates. J Neuroendocrinol. 2022 May;34(5):e13119. doi:10.1111/jne.13119. EUR J MED HEALTH RES Volume 3 | Number 6 | 2025 99 [5] Lanciotti L, Cofini M, Leonardi A, Penta L, Esposito S. Up-to-date review about minipuberty and overview on hypothalamic-pituitary-gonadal axis activation in fetal and neonatal life. Front Endocrinol (Lausanne). 2018;9:410. doi:10.3389/fendo.2018.00410. [6] Datta A, Datta A. Supernumerary nostril, proboscis lateralis and polyrhinia. Eur J Med Health Res. 2024;2(2):201-205. doi:10.59324/ejmhr.2024.2(2).22. [7] Ojeda SR, Andrews WW, Advis JP, White SS. Recent advances in the endocrinology of puberty. Endocr Rev. 1980 Summer;1(3):228-257. doi:10.1210/edrv-1-3-228.