The pulsatile secretion of gonadotropin-releasing hormone (GnRH) release is an intrinsic property of hypothalamic GnRH neurons and attributed to several specific mechanisms. These include the spontaneous electrical activity of GnRH neurons, calcium and cAMP signaling, a GnRH receptor autocrine regulatory component, a GnRH concentration-dependent switch in GnRH receptor (GnRH-R) coupling to specific G proteins, expression of G protein-coupled receptors (GPCRs) and steroid receptors, and homologous and heterologous interactions between cell-membrane receptors expressed in GnRH neurons. The coexistence of multiple regulatory mechanisms for pulsatile GnRH secretion provides a high degree of redundancy in maintaining this crucial component of the mammalian reproductive process. These studies provided insights into the basic cellular and molecular mechanisms involved in GnRH neuronal function. Hypothalamic control of reproductive functionThe episodic mode of GnRH secretion from the hypothalamus and of GnRH receptor (GnRH-R) activation in pituitary gonadotrophs are essential for optimal gonadotropin synthesis and secretion and ultimately for normal reproductive function [1][2][3][4][5]. The genesis of GnRH pulse generation in the hypothalamus is still incompletely understood. However, episodic neuropeptide secretion is an intrinsic property of the GnRH neuron and dependent on intracellular signaling and mechanism(s) leading to coordinated bursts of GnRH release [5][6][7][8][9][10][11][12]. Seminal studies by Ernst Knobil et al. in rhesus monkeys defined the importance of episodic pituitary stimulation for optimal gonadotropin secretion, as well as the relationship of GnRH release to electrical activity in the hypothalamus and the essential role of estrogen in promoting the mid-cycle LH surge [13,14].The neuroendocrine control of reproductive function is expressed through the episodic secretion of gonadotropic hormones from the anterior pituitary gland in response to pulsatile stimulation by GnRH, produced by a network of peptidergic neurons in the hypothalamus [11,[15][16][17][18][19][20]. The characteristic pulsatile secretion of GnRH from hypothalamic neurons is dependent on an autocrine interaction between GnRH and its receptors expressed in GnRHproducing neurons. It is noteworthy that GnRH-R expression, GnRH-dependent activation of Ca 2+ signaling, and autocrine regulation of GnRH release are evident in early fetal GnRH neurons. It is probable that such activity provides a mechanism for gene expression and regulated GnRH secretion during embryonic migration [21][22][23].Crown

Context and PurposeMeasurement‐based care (MBC) is an evidence‐based health‐care practice in which indicators of disease are tracked to inform clinical actions, provide feedback to patients and improve outcomes. The current opioid crisis in multiple countries provides a pressing rationale for adopting a basic MBC approach for opioid use disorder (OUD) using DSM‐5 to increase treatment retention and effectiveness.ProposalTo stimulate debate, we propose a basic MBC approach using the 11 symptoms of OUD (DSM‐5) to inform the delivery of medications for opioid use disorder (MOUD; including methadone, buprenorphine and naltrexone) and their evaluation in office‐based primary care and specialist clinics. Key features of a basic MBC approach for OUD using DSM‐5 are described, with an illustration of how clinical actions are guided and outcomes communicated. For core treatment tasks, we propose that craving and drug use response to MOUD should be assessed after 2 weeks, and OUD remission status should be evaluated at 3, 6 and 12 months (and exit from MOUD treatment) and beyond. Each of the 11 DSM‐5 symptoms of OUD should be discussed with the patient to develop a case formulation and guide selection of adjunctive psychological interventions, supplemented with information on substance use, and optionally extended with information from other clinical instruments. A patient‐reported outcome measure should be recorded and discussed at each remission assessment.ConclusionsMBC can be used to tailor and adapt MOUD treatment to increase engagement, retention and effectiveness. MBC practice principles can help promote patient‐centred care in OUD, personalized addiction therapeutics and facilitate communication of outcomes.