Hypothalamus/Pituitary - Reproduction Neuroendocrinology

Flashcards cover GnRH production sites, pulse regulation, feedback by estradiol and progesterone, KNDy neural network, and related hypothalamic-pituitary anatomy and pharmacology.

GnRH (Gonadotropin-Releasing Hormone)

Hypothalamic decapeptide that stimulates the anterior pituitary to release FSH and LH; produced by GnRH neurons in the POA and ARC; released in pulses into the median eminence.

GnRH Neurons

Specialized neurons that regulate reproduction; integrate multiple signals and generate pulsatile GnRH to drive FSH/LH secretion.

POA (Preoptic Area)

Hypothalamic region; surge center; mediates estradiol-positive feedback leading to GnRH surge and ovulation.

ARC (Arcuate Nucleus)

Hypothalamic nucleus; tonic center; mediates negative feedback of estradiol and progesterone and drives GnRH pulse generation via KNDy neurons.

AVPV (Anteroventral Periventricular Nucleus)

Surge center in the hypothalamus; mediates positive feedback of estradiol to promote GnRH/LH surge.

KNDy Neurons

ANetwork of GnRH-regulating neurons that co-express Kisspeptin, Neurokinin B, and Dynorphin; upstream drivers of GnRH pulses.

Kisspeptin

Neuropeptide that directly stimulates GnRH release; essential for GnRH pulse generation; receptor mutations can cause hypogonadism.

Neurokinin B (NKB)

Neurokinin B; stimulates kisspeptin release; part of the KNDy network driving GnRH pulses.

Dynorphin

Opioid peptide that inhibits Neurokinin B/kisspeptin release within the KNDy network; helps regulate GnRH pulse timing.

Median Eminence

Hypothalamic release site where GnRH enters the portal circulation to the anterior pituitary.

Anterior Pituitary

Gland that secretes FSH and LH in response to GnRH pulses.

Posterior Pituitary

Neural-tissue region that stores and releases oxytocin and vasopressin; prolactin is secreted by the anterior pituitary.

Pulsatile GnRH Secretion

Pattern of GnRH release in discrete pulses; essential for maintaining FSH/LH synthesis and secretion.

LH Pulses

Pulses of luteinizing hormone in the bloodstream; used as a proxy to infer GnRH pulse activity.

Estradiol – Negative Feedback

High/early estradiol levels mainly exert negative feedback on GnRH neurons via the ARC (tonic center) to reduce GnRH pulses.

Estradiol – Positive Feedback

High estradiol levels in certain contexts stimulate the surge center (POA/AVPV) to trigger GnRH/LH surge and ovulation.

Progesterone

Steroid that helps maintain homeostasis by reducing GnRH pulse frequency; participates in negative feedback with estradiol.

Tonic Center

ARC-mediated center providing negative feedback and generating relatively frequent GnRH pulses.

Surge Center

POA/AVPV-mediated center providing positive feedback and driving the GnRH/LH surge for ovulation.

GNRH Pulse Frequency

The rate of GnRH pulses; higher frequency favors continuous activation of LH/FSH release, while low frequency differently modulates response.

GnRH Agonist

Compounds that mimic GnRH; initially stimulate pituitary, then cause desensitization and suppression of gonadotropin release (e.g., leuprolide).

GnRH Antagonist

Block GnRH receptors, rapidly suppressing gonadotropin release (e.g., degarelix).

Nobel Prize 1977 (GnRH)**

Guillemin and Schally recognized for isolating GnRH and determining its structure (LHRH).

Estradiol Effects on Feedback

Estradiol can exert both negative feedback (ARC/tonic center) and positive feedback (POA/AVPV surge center) depending on context and concentration.

Gonadotropin Role of Pulsatility

Pulsatile GnRH is required for pituitary FSH/LH function; continuous GnRH exposure desensitizes receptors and suppresses gonadotropin release.

Hypothalamic Areas for GnRH Regulation

POA (surge center) and ARC (tonic center) are key hypothalamic regions mediating positive and negative feedback on GnRH.

Are GnRH Pulses Intrinsic?

Yes; GnRH pulses are intrinsic to the hypothalamus and rely on KNDy neuron activity rather than GnRH neurons alone.

Isestrous Measurements of Pulses

LH pulses in peripheral blood are used as a proxy for GnRH pulses; ex vivo hypothalamic tissue can still generate GnRH pulses.