Hypothalamic but not pituitary or ovarian defects underlie the reproductive abnormalities in Axl/Tyro3 null mice.

AXL and TYRO3, members of the TYRO3, AXL and MER (TAM) family of tyrosine kinase receptors, modulate GnRH neuronal cell migration, survival and gene expression. Axl/Tyro3 null mice exhibit a selective loss of GnRH neurons, delayed sexual maturation and irregular estrous cycles. Here we determined whether the defects were due to direct ovarian defects, altered pituitary sensitivity to GnRH and/or an impaired LH surge mechanism. Ovarian histology and markers of folliculogenesis and atresia as well as corpora luteal development and ovarian response to superovulation were not impaired. Axl/Tryo3 null mice exhibited a robust LH response to exogenous GnRH, suggesting no altered pituitary sensitivity. Ovariectomized Axl/Tyro3 null mice, however, demonstrated an impaired ability to mount a steroid-induced LH surge. Loss of GnRH neurons in Axl/Tyro3 null mice impairs the sex hormone-induced gonadotropin surge resulting in estrous cycle abnormalities confirming that TAM family members contribute to normal female reproductive function.

Summary of the recommendations on sexual dysfunctions in women.

INTRODUCTION: Women's sexual dysfunction includes reduced interest/incentives for sexual engagement, difficulties with becoming subjectively and/or genitally aroused, difficulties in triggering desire during sexual engagement, orgasm disorder, and sexual pain. AIM: To update the recommendations published in 2004, from the 2nd International Consultation on Sexual Medicine (ICSM) pertaining to the diagnosis and treatment of women's sexual dysfunctions. METHODS: A third international consultation in collaboration with the major sexual medicine associations assembled over 186 multidisciplinary experts from 33 countries into 25 committees. Twenty one experts from six countries contributed to the Recommendations on Sexual Dysfunctions in Women. MAIN OUTCOME MEASURE: Expert opinion was based on grading of evidence-based medical literature, widespread internal committee discussion, public presentation, and debate. RESULTS: A comprehensive assessment of medical, sexual, and psychosocial history is recommended for diagnosis and management. Indications for general and focused pelvic genital examination are identified. Evidence based recommendations for further revisions of definitions for sexual disorders are given. An evidence based approach to management is provided. Extensive references are provided in the full ICSM reports. CONCLUSIONS: There remains a need for more research and scientific reporting on the optimal management of women's sexual dysfunctions including multidisciplinary approaches.

The role of gonadotropin releasing hormone in normal and pathologic endocrine processes.

PURPOSE OF REVIEW: Gonadotropin releasing hormone is the hypothalamic hormone that activates pituitary gonadotropin production and, ultimately, determines reproductive competence. This review will highlight advances in the basic biology of the gonadotropin releasing hormone neuron that give insight into disorders of pubertal development, and clinical studies with gonadotropin releasing hormone analogs in infertility and prostate cancer treatment. RECENT FINDINGS: Factors that control gonadotropin releasing hormone neuronal migration such as fibroblast growth factor receptor-1 and others that modulate secretion at puberty including kisspeptin/G-protein-coupled receptor 54 have been identified. Mutations in these pathways cause disorders during puberty. Clinical trials have defined the utility of gonadotropin releasing hormone agonists and antagonists for ovulation induction, and the effects of long-term administration for prostate cancer. SUMMARY: Research into the role of the fibroblast growth factor receptor-1 and kisspeptin/G-protein-coupled receptor 54 pathways in gonadotropin releasing hormone neuronal development may identify the molecular defects in idiopathic hypogonadotropic hypogonadism and refine our understanding of normal negative and positive feedback by sex steroids. Clarification of the advantages and disadvantages of gonadotropin releasing hormone analog use in ovulation induction may improve the cost and success of infertility treatment. Insight into long-term effects of gonadotropin releasing hormone analogs in prostate cancer may lead to directed therapies to combat these consequences. Together these studies outline effects of modulation of gonadotropin releasing hormone in normal and pathophysiologic states.