Brain Structure and Function

, Volume 225, Issue 1, pp 241–248 | Cite as

Presence of substance P positive terminals on hypothalamic somatostatinergic neurons in humans: the possible morphological substrate of the substance P-modulated growth hormone secretion

  • Andrew Luu
  • Zachary Oberdoerster
  • George Grignol
  • Istvan MerchenthalerEmail author
  • Bertalan Dudas
Original Article


Substance P is an undecapeptide affecting the gastrointestinal, cardiovascular, and urinary systems. In the central nervous system, substance P participates in the regulation of pain, learning, memory, and sexual homeostasis. In addition to these effects, previous papers provided solid evidence that substance P exhibits regulatory effects on growth. Indeed, our previous study revealed that growth hormone-releasing hormone (GHRH) neurons appear to be densely innervated by substance P fibers in humans. Since growth hormone secretion is regulated by the antagonistic actions of both GHRH and somatostatin, in the present paper we have examined the possibility that SP may also affect growth via the somatostatinergic system. Therefore, we have studied the putative presence of juxtapositions between the substance P-immunoreactive (IR) and somatostatinergic systems utilizing double label immunohistochemistry combined with high magnification light microscopy with oil immersion objective. In the present study, we have revealed a dense network of substance P-IR axonal varicosities contacting the majority of somatostatin-IR neurons in the human hypothalamus. Somatostatinergic perikarya are often covered by these fiber varicosities that frequently form basket-like encasements with multiple en passant type contacts, particularly in the infundibular nucleus/median eminence and in the basal periventricular area of the tuberal region. In addition, numerous substance-P-somatostatinergic juxtapositions can be found in the basal perifornical zone of the tuberal area. If these contacts are indeed functional synapses, they may represent the morphological substrate of the control of substance P on growth. Indeed, the frequency and density of these juxtapositions indicate that in addition to the regulatory action of substance P on GHRH secretion, substance P also influences growth by regulating hypothalamic somatostatinergic system via direct synaptic contacts.


Substance P Somatostatin Juxtaposition Immunohistochemistry Human hypothalamus 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants

The brain utilized in these studies was harvested 12 h post mortem period in accordance with the regulations of the Institutional Review Board of Lake Erie College of Osteopathic Medicine (LECOM). See materials and methods.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Andrew Luu
    • 1
  • Zachary Oberdoerster
    • 1
  • George Grignol
    • 1
  • Istvan Merchenthaler
    • 2
    Email author
  • Bertalan Dudas
    • 1
  1. 1.Neuroendocrine Organization Laboratory (NEO)Lake Erie College of Osteopathic Medicine (LECOM)ErieUSA
  2. 2.Department of Epidemiology and Public Health and Anatomy and NeurobiologyUniversity of Maryland BaltimoreBaltimoreUSA

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