Gonadotrophin-Releasing Hormone Pulse Generator Activity in the Hypothalamus of the Goat

• Published in: Journal of neuroendocrinology Vol. 21; no. 10; pp. 813 - 821
• Main Authors: Ohkura, S., Takase, K., Matsuyama, S., Mogi, K., Ichimaru, T., Wakabayashi, Y., Uenoyama, Y., Mori, Y., Steiner, R. A., Tsukamura, H., Maeda, K.-I., Okamura, H.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2009; Blackwell
• Subjects: Amino Acid Sequence; Animals; Arcuate Nucleus of Hypothalamus - physiology; Biological and medical sciences; Electrodes, Implanted; Fundamental and applied biological sciences. Psychology; Goats; Gonadotropin-Releasing Hormone - secretion; Humans; hypothalamus; Hypothalamus - physiology; Immunohistochemistry; In Situ Hybridization; kisspeptin; Kisspeptins; luteinising hormone; Luteinizing Hormone - blood; Male; Molecular Sequence Data; multiple-unit activity; Neural Pathways - physiology; Neurons - physiology; Orchiectomy; Periodicity; ruminant; Sequence Homology, Amino Acid; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Vertebrates: endocrinology; ruminant; luteinising hormone; Central nervous system; Gonadotropin RH; Hypothalamus; Encephalon; Hypothalamic hormone; Kisspeptin; Vertebrata; Mammalia; Animal; multiple-unit activity; Goat; Artiodactyla; Hormone releasing factor; Ungulata
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2009.01909.x

Pulsatile release of gonadotrophin‐releasing hormone (GnRH) is indispensable to maintain normal gonadotrophin secretion. The pulsatile secretion of GnRH is associated with synchronised electrical activity in the mediobasal hypothalamus (i.e. multiple unit activity; MUA), which is considered to reflect the rhythmic oscillations in the activity of the neuronal network that drives pulsatile GnRH secretion. However, the cellular source of this ultradian rhythm in GnRH activity is unknown. Direct input from kisspeptin neurones in the arcuate nucleus (ARC) to GnRH cell bodies in the medial preoptic area or their terminals in the median eminence could be the intrinsic source for driving the GnRH pulse generator. To determine whether kisspeptin signalling could be responsible for producing pulsatile GnRH secretion, we studied goats, measured plasma levels of luteinising hormone (LH) and recorded MUA in the posterior ARC, where the majority of kisspeptin neuronal cell bodies are located. Rhythmic volleys of MUA were found to be accompanied by LH pulses with regular intervals in the ARC, where kisspeptin neuronal cell bodies were found. Exogenous administration of kisspeptin stimulated a sustained increase in LH secretion, without influencing MUA, suggesting that the GnRH pulse generator, as reflected by MUA, originated from outside of the network of GnRH neurones, and could plausibly reflect the pacemaker activity of kisspeptin neurones, whose projections reach the median eminence where GnRH fibres project. These observations suggest that the kisspeptin neurones in the ARC may be the intrinsic source of the GnRH pulse generator.