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Search: authors:"Seminara, Stephanie B."

29 papers found.
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Continuous Kisspeptin Administration in Postmenopausal Women: Impact of Estradiol on Luteinizing Hormone Secretion

Kisspeptin stimulates the reproductive endocrine cascade in both men and women. Circulating sex steroids are thought to modulate the ability of kisspeptin to stimulate gonadotropin-releasing hormone (GnRH)–induced luteinizing hormone (LH) release.

Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty

Some patients with idiopathic hypogonadotropic hypogonadism (IHH) undergo spontaneous activation of their hypothalamic-pituitary-gonadal axis resulting in normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal.

Neurokinin B Is Critical for Normal Timing of Sexual Maturation but Dispensable for Adult Reproductive Function in Female Mice

Humans carrying mutations in neurokinin B (NKB) or the NKB receptor fail to undergo puberty due to decreased secretion of GnRH. Despite this pubertal delay, many of these patients go on to achieve activation of their hypothalamic-pituitary-gonadal axis in adulthood, a phenomenon termed reversal, indicating that NKB signaling may play a more critical role for the timing of...

Kisspeptin and the Hypothalamic Control of Reproduction: Lessons from the Human

The hypothalamic hormone GnRH is a central driver of pituitary gonadotropin secretion, controlling pulsatile gonadotropin secretion, modulating gonadal steroid feedback, and bringing about full fertility in the adult. Thus, understanding GnRH neuronal regulation is essential to understanding the neurohumoral control of human reproduction. Genetic tools were used in patients with...

A Shared Genetic Basis for Self-Limited Delayed Puberty and Idiopathic Hypogonadotropic Hypogonadism

Delayed puberty (DP) is a common issue and, in the absence of an underlying condition, is typically self limited. Alhough DP seems to be heritable, no specific genetic cause for DP has yet been reported. In contrast, many genetic causes have been found for idiopathic hypogonadotropic hypogonadism (IHH), a rare disorder characterized by absent or stalled pubertal development.

The Integrated Hypothalamic Tachykinin-Kisspeptin System as a Central Coordinator for Reproduction

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of...

Kisspeptin Resets the Hypothalamic GnRH Clock in Men

Reproduction in all mammals is controlled by a hypothalamic clock that produces periodic secretory pulses of GnRH, but how the timing of these pulses is determined is poorly understood. The neuropeptide kisspeptin potently and selectively stimulates the secretion of GnRH. Although this property of kisspeptin is well described, the effects of kisspeptin on endogenous GnRH pulse...

Responsiveness to a Physiological Regimen of GnRH Therapy and Relation to Genotype in Women With Isolated Hypogonadotropic Hypogonadism

Isolated hypogonadotropic hypogonadism (IHH) is caused by defective GnRH secretion or action resulting in absent or incomplete pubertal development and infertility. Most women with IHH ovulate with physiological GnRH replacement, implicating GnRH deficiency as the etiology. However, a subset does not respond normally, suggesting the presence of defects at the pituitary or ovary.

The Role of the Prokineticin 2 Pathway in Human Reproduction: Evidence from the Study of Human and Murine Gene Mutations

A widely dispersed network of hypothalamic GnRH neurons controls the reproductive axis in mammals. Genetic investigation of the human disease model of isolated GnRH deficiency has revealed several key genes crucial for GnRH neuronal ontogeny and GnRH secretion. Among these genes, prokineticin 2 (PROK2), and PROK2 receptor (PROKR2) have recently emerged as critical regulators of...

Genetic Approaches to Unraveling Reproductive Disorders: Examples of Bedside to Bench Research in the Genomic Era

Despite the rapid advances in medical genetics, many clinicians and investigators remain unaware of the general approaches that can be used to map genes. Although there are specific challenges to using genetic approaches in reproductive medicine, the following report summarizes mapping efforts for three diseases: adrenal hypoplasia congenita, hypergonadotropic ovarian failure...

Prioritizing Genetic Testing in Patients With Kallmann Syndrome Using Clinical Phenotypes

The complexity of genetic testing in Kallmann syndrome (KS) is growing and costly. Thus, it is important to leverage the clinical evaluations of KS patients to prioritize genetic screening.

Expanding the Phenotype and Genotype of Female GnRH Deficiency

GnRH deficiency is a rare genetic disorder of absent or partial pubertal development. The clinical and genetic characteristics of GnRH-deficient women have not been well-described.

Expanding the Phenotype and Genotype of Female GnRH Deficiency

GnRH deficiency is a rare genetic disorder of absent or partial pubertal development. The clinical and genetic characteristics of GnRH-deficient women have not been well-described.