Michael N. Lehman
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View article: A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations
A compilation of 13 patients with metastatic colorectal cancer and concomitant BRAF and RAS family mutations Open
Introduction Metastatic colorectal cancer (mCRC) exhibits significant heterogeneity in molecular profiles, influencing treatment response and patient outcomes. Mutations in v-raf murine sarcoma viral oncogene homolog B1 ( BRAF ) and rat sa…
View article: How Might a ‘Philosopher's Toolkit’ Help Advance Neuroscience? Let's Ask Some Neuroscientists
How Might a ‘Philosopher's Toolkit’ Help Advance Neuroscience? Let's Ask Some Neuroscientists Open
In the terms adopted by the editors of this special issue concerning how a ‘philosopher's toolkit’ might contribute to progress in neuroscience, this paper reports posing that question to several neuroscientists, all with a track record of…
View article: Critical role of arcuate nucleus kisspeptin and <scp>Kiss1R</scp> in regulation of the ovine luteinizing hormone surge
Critical role of arcuate nucleus kisspeptin and <span>Kiss1R</span> in regulation of the ovine luteinizing hormone surge Open
Hypothalamic kisspeptin (Kiss), neurokinin B (NKB), and dynorphin‐containing (KNDy) neurons in the arcuate nucleus (ARC) have consistently been shown to be the central generator of gonadotropin‐releasing hormone (GnRH) and corresponding lu…
View article: How might a “philosopher’s toolkit” help advance neuroscience? Let’s ask some neuroscientists
How might a “philosopher’s toolkit” help advance neuroscience? Let’s ask some neuroscientists Open
How might a "philosopher's toolkit" contribute to progress in neuroscience? This paper addresses this question by first posing it to several neuroscientists, all with a track record of successfully interacting with philosophers. These disc…
View article: KNDy Neurons of the Hypothalamus and Their Role in GnRH Pulse Generation: an Update
KNDy Neurons of the Hypothalamus and Their Role in GnRH Pulse Generation: an Update Open
There is considerable evidence that synchronized activity within a reciprocally connected population of cells in the arcuate nucleus (ARC) coexpressing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy cells) is crucial for the generatio…
View article: 25 Role of Kndy and Arcuate Kiss1r-Containing Neurons in the Preovulatory Luteinizing Hormone Surge and Puberty Onset of Female sheep
25 Role of Kndy and Arcuate Kiss1r-Containing Neurons in the Preovulatory Luteinizing Hormone Surge and Puberty Onset of Female sheep Open
Neurons within the arcuate nucleus (ARC) of the hypothalamus containing kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons) have an important role in regulating the pulsatile secretion of gonadotropin releasing hormone (GnRH) and …
View article: Lesions of KNDy and Kiss1R Neurons in the Arcuate Nucleus Produce Different Effects on LH Pulse Patterns in Female Sheep
Lesions of KNDy and Kiss1R Neurons in the Arcuate Nucleus Produce Different Effects on LH Pulse Patterns in Female Sheep Open
The current model for the synchronization of GnRH neural activity driving GnRH and LH pulses proposes that a set of arcuate (ARC) neurons that contain kisspeptin, neurokinin B, and dynorphin (KNDy neurons) is the GnRH pulse generator. This…
View article: KNDy neurons as the GnRH pulse generator: Recent studies in ruminants
KNDy neurons as the GnRH pulse generator: Recent studies in ruminants Open
View article: Prenatal androgen treatment impairs the suprachiasmatic nucleus arginine-vasopressin to kisspeptin neuron circuit in female mice
Prenatal androgen treatment impairs the suprachiasmatic nucleus arginine-vasopressin to kisspeptin neuron circuit in female mice Open
Polycystic ovary syndrome (PCOS) is associated with elevated androgen and luteinizing hormone (LH) secretion and with oligo/anovulation. Evidence indicates that elevated androgens impair sex steroid hormone feedback regulation of pulsatile…
View article: Interviews: A collection of stories and perspectives about the past and future of <scp>GnRH</scp> research
Interviews: A collection of stories and perspectives about the past and future of <span>GnRH</span> research Open
As an endpiece to this Special Issue celebrating the 50th anniversary of the discovery of GnRH, we asked a group of luminaries in this area of neuroendocrine research to consider the past and future of GnRH research.The following questions…
View article: In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse
In vivo imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse Open
Significance Hypothalamic oscillators that generate pulsatile patterns of hormone secretion represent a fundamental physiological feature regulating homeostatic systems. How individual cells within these neural ensembles generate and coord…
View article: Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion
Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion Open
The concept that different systems control episodic and surge secretion of gonadotropin‐releasing hormone (GnRH) was well established by the time that GnRH was identified and formed the framework for studies of the physiological roles of G…
View article: Author response for "Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion"
Author response for "Neuroendocrine control of gonadotropin‐releasing hormone: Pulsatile and surge modes of secretion" Open
View article: <i>In vivo</i>imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse
<i>In vivo</i>imaging of the GnRH pulse generator reveals a temporal order of neuronal activation and synchronization during each pulse Open
A hypothalamic pulse generator located in the arcuate nucleus controls episodic release of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) and is essential for reproduction. Recent evidence suggests this generator is com…
View article: Prenatal Androgen Exposure Alters KNDy Neurons and Their Afferent Network in a Model of Polycystic Ovarian Syndrome
Prenatal Androgen Exposure Alters KNDy Neurons and Their Afferent Network in a Model of Polycystic Ovarian Syndrome Open
Polycystic ovarian syndrome (PCOS), the most common endocrinopathy affecting women worldwide, is characterized by elevated luteinizing hormone (LH) pulse frequency due to the impaired suppression of gonadotrophin-releasing hormone (GnRH) r…
View article: Localization of kisspeptin, NKB, and NK3R in the hypothalamus of gilts treated with the progestin altrenogest
Localization of kisspeptin, NKB, and NK3R in the hypothalamus of gilts treated with the progestin altrenogest Open
Mechanisms in the brain controlling secretion of gonadotropin hormones in pigs, particularly luteinizing hormone (LH), are poorly understood. Kisspeptin is a potent LH stimulant that is essential for fertility in many species, including pi…
View article: Food Entrainment, Arousal, and Motivation in the Neonatal Rabbit Pup
Food Entrainment, Arousal, and Motivation in the Neonatal Rabbit Pup Open
In the newborn rabbit, the light entrainable circadian system is immature and once a day nursing provides the primary timing cue for entrainment. In advance of the mother’s arrival, pups display food anticipatory activity (FAA), and metabo…
View article: Evidence that synaptic plasticity of glutamatergic inputs onto KNDy neurones during the ovine follicular phase is dependent on increasing levels of oestradiol
Evidence that synaptic plasticity of glutamatergic inputs onto KNDy neurones during the ovine follicular phase is dependent on increasing levels of oestradiol Open
Neurones in the arcuate nucleus co‐expressing kisspeptin, neurokinin B (NKB) and dynorphin (KNDy) play a critical role in the control of gonadotrophin‐releasing hormone (GnRH) and luteinising hormone (LH) secretion. In sheep, KNDy neurones…
View article: Morphological and functional evidence for sexual dimorphism in neurokinin B signalling in the retrochiasmatic area of sheep
Morphological and functional evidence for sexual dimorphism in neurokinin B signalling in the retrochiasmatic area of sheep Open
Neurokinin B (NKB) is critical for fertility in humans and stimulates gonadotrophin‐releasing hormone/luteinising hormone (LH) secretion in several species, including sheep. There is increasing evidence that the actions of NKB in the retro…
View article: Evidence that Nitric Oxide Is Critical for LH Surge Generation in Female Sheep
Evidence that Nitric Oxide Is Critical for LH Surge Generation in Female Sheep Open
Elevated and sustained estradiol concentrations cause a gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) surge that is necessary for ovulation. In sheep, several different neural systems have been implicated in this stimu…
View article: Role for Kisspeptin and Neurokinin B in Regulation of Luteinizing Hormone and Testosterone Secretion in the Fetal Sheep
Role for Kisspeptin and Neurokinin B in Regulation of Luteinizing Hormone and Testosterone Secretion in the Fetal Sheep Open
Evidence suggests that the hypothalamic–pituitary–gonadal (HPG) axis is active during the critical period for sexual differentiation of the ovine sexually dimorphic nucleus, which occurs between gestational day (GD) 60 and 90. Two possible…
View article: Importance of neuroanatomical data from domestic animals to the development and testing of the KNDy hypothesis for GnRH pulse generation
Importance of neuroanatomical data from domestic animals to the development and testing of the KNDy hypothesis for GnRH pulse generation Open
View article: Kisspeptin/Neurokinin B/Dynorphin (KNDy) cells as integrators of diverse internal and external cues: evidence from viral-based monosynaptic tract-tracing in mice
Kisspeptin/Neurokinin B/Dynorphin (KNDy) cells as integrators of diverse internal and external cues: evidence from viral-based monosynaptic tract-tracing in mice Open
View article: Evidence That the LH Surge in Ewes Involves Both Neurokinin B–Dependent and –Independent Actions of Kisspeptin
Evidence That the LH Surge in Ewes Involves Both Neurokinin B–Dependent and –Independent Actions of Kisspeptin Open
Recent evidence has implicated neurokinin B (NKB) signaling in the retrochiasmatic area (RCh) of the ewe in the LH surge. To test this hypothesis, we first lesioned NK3R neurons in this area by using a saporin conjugate (NK3-SAP). Three we…
View article: Prenatal Testosterone Exposure Alters GABAergic Synaptic Inputs to GnRH and KNDy Neurons in a Sheep Model of Polycystic Ovarian Syndrome
Prenatal Testosterone Exposure Alters GABAergic Synaptic Inputs to GnRH and KNDy Neurons in a Sheep Model of Polycystic Ovarian Syndrome Open
Prenatal testosterone (T)-treated female sheep display reproductive deficits similar to women with polycystic ovarian syndrome (PCOS), including an increase in LH pulse frequency due to actions of the central GnRH pulse generator. In this …
View article: The role of kisspeptin in reproductive function in the ewe
The role of kisspeptin in reproductive function in the ewe Open
Summary Kisspeptin is a hypothalamic neuropeptide that is critical for fertility. In virtually all species, kisspeptin neurons stimulate gonadotrophin-releasing hormone (GnRH) secretion and act as transmitters for sex-steroid feedback to G…
View article: SAT-426 Rabies-Mediated Monosynaptic Tract-Tracing of Sexually Dimorphic Estrogen-Sensitive Afferents to KNDy Neurons in the Mouse
SAT-426 Rabies-Mediated Monosynaptic Tract-Tracing of Sexually Dimorphic Estrogen-Sensitive Afferents to KNDy Neurons in the Mouse Open
Estradiol controls reproductive status and sexual behavior by acting upon a variety of neurochemical systems in the brain to mediate the sexually dimorphic release of gonadotrophins. However, the neural pathways that transmit steroid hormo…
View article: SAT-421 Cell-Specific Ablation of GnRH Neurons Using Kisspeptin-Saporin in the Preoptic Area of Sheep, but Not Mice
SAT-421 Cell-Specific Ablation of GnRH Neurons Using Kisspeptin-Saporin in the Preoptic Area of Sheep, but Not Mice Open
Sheep have been a useful preclinical model for the exploration of the role of kisspeptin and its receptor, KISS1R, in the control of pulsatile section of gonadotropin releasing hormone (GnRH). However, lack of reagents to interrogate KISS1…
View article: Does the KNDy Model for the Control of Gonadotropin-Releasing Hormone Pulses Apply to Monkeys and Humans?
Does the KNDy Model for the Control of Gonadotropin-Releasing Hormone Pulses Apply to Monkeys and Humans? Open
There is now considerable evidence supporting the role of a subpopulation of neurons in the arcuate nucleus of the hypothalamus that coexpress kisspeptin, neurokinin B, and dynorphin (abbreviated as KNDy neurons) as the long sought-after g…
View article: Evidence That Dynorphin Acts Upon KNDy and GnRH Neurons During GnRH Pulse Termination in the Ewe
Evidence That Dynorphin Acts Upon KNDy and GnRH Neurons During GnRH Pulse Termination in the Ewe Open
A subpopulation of neurons located within the arcuate nucleus, colocalizing kisspeptin, neurokinin B, and dynorphin (Dyn; termed KNDy neurons), represents key mediators of pulsatile GnRH secretion. The KNDy model of GnRH pulse generation p…