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Abstract
Neurons synthesizing neurokinin B (NKB) and kisspeptin (KP) in the hypothalamic arcuate nucleus represent important upstream regulators of pulsatile gonadotropin-releasing hormone (GnRH) neurosecretion. In search of neuropeptides co-expressed in analogous neurons of the human infundibular nucleus (Inf), we have carried out immunohistochemical studies of the tachykinin peptide Substance P (SP) in autopsy samples from men (21-78 years) and postmenopausal (53-83 years) women. Significantly higher numbers of SP-immunoreactive (IR) neurons and darker labeling were observed in the Inf of postmenopausal women than in age-matched men. Triple-immunofluorescent studies localized SP immunoreactivity to considerable subsets of KP-IR and NKB-IR axons and perikarya in the infundibular region. In postmenopausal women, 25.1% of NKB-IR and 30.6% of KP-IR perikarya contained SP and 16.5% of all immunolabeled cell bodies were triple-labeled. Triple-, double- and single-labeled SP-IR axons innervated densely the portal capillaries of the infundibular stalk. In quadruple-labeled sections, these axons formed occasional contacts with GnRH-IR axons. Presence of SP in NKB and KP neurons increases the functional complexity of the putative pulse generator network. First, it is possible that SP modulates the effects of KP and NKB in axo-somatic and axo-dendritic afferents to GnRH neurons. Intrinsic SP may also affect the activity and/or neuropeptide release of NKB and KP neurons via autocrine/paracrine actions. In the infundibular stalk, SP may influence the KP and NKB secretory output via additional autocrine/paracrine mechanisms or regulate GnRH neurosecretion directly. Finally, possible co-release of SP with KP and NKB into the portal circulation could underlie further actions on adenohypophysial gonadotrophs.
Highlights
The hypothalamic arcuate nucleus (ARC) plays a pivotal role in reproductive regulation [1]
In this study we provide immunohistochemical evidence that Substance P (SP)-IR neurons are present in higher numbers in the infundibular nucleus (Inf) of postmenopausal women compared with age-matched men
Our main observation is the frequent coexpression of SP immunoreactivity in KP-IR and neurokinin B (NKB)-IR neuronal cell bodies and fibers in the human infundibular region
Summary
The hypothalamic arcuate nucleus (ARC) plays a pivotal role in reproductive regulation [1]. While it is tempting to make predictions about the neuroanatomy and functions of a putative human ‘KNDy’ neuronal system from the known properties of the rodent or ruminant KNDy neurons, direct extrapolation from the results of animal experiments is not always possible as there can be significant species differences in the hypothalamic regulation of reproduction. Several neurochemical differences have already been revealed between the human and the animal KP and NKB neuronal systems. Differences between animal and human neuroanatomy and reproductive physiology call for further studies to identify other neurotransmitters/neuromodulators which may co-localize with the human KP and NKB neuronal systems
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