Question

The production of a GnRH/LH surge in response to high levels of estradiol is sexually differentiated in most mammals, i.e. in males castrated to remove negative feedback from endogenous testosterone, treatment with a dose of estradiol that is known to elicit a GnRH and LH surge in ovariectomized females does not produce a GnRH or LH surge. Differentiation of the surge response is due to the effects of gonadal steroids acting on the developing brain.

Based on your understanding of prenatal secretion of steroids, speculate what happens in males vs. females that results in the presence or absence of a GnRH/LH surge response. Suggest two prenatal treatments that might be used to test the validity of your explanation – one that disrupts the LH surge in females, and one that yields a functional surge response in males. In other words, what substance could be administered to a pregnant female that might produce female offspring in which high levels of estradiol do not produce a GnRH/LH surge, and what substance could be administered that might produce male offspring in which high levels of estradiol do produce a GnRH/LH surge?

Answer 1

Two distinct modes of GnRH secretion have been described: pulsatile and surge modes:

Pulsatile mode refers to episodic release of GnRH, where there are distinct pulses of GnRH secretion into the portal circulation with undetectable GnRH concentrations during inter-pulse intervals.A pulsatile pattern of GnRH secretion was demonstrated subsequently in humans through serial blood sampling during pituitary surgery

The surge mode of GnRH secretion occurs in females during the pre-ovulatory phase in which the presence of GnRH in the portal circulation appears to be persistent.

In women, the frequency and amplitude of LH pulses were noted to be dependent on the menstrual cycle phase, with pulses every 1 to 2 hours during the early follicular phase eventually merging into a continuous mid-cycle surge, and decreased pulse frequency to every 4 hours during the luteal phase

In human beings the LH pulse frequency is now used as a surrogate of GnRH pulsatility, as ethical considerations and technical challenges preclude sampling of hypophyseal blood or cerebrospinal fluid to measure GnRH concentrations directly

Functionally, the ‘GnRH pulse generator’ relies on complex relations between glutamatergic cells, GnRH and other neurons, and likely other elements are involved, of which the kisspeptin-neurokinin B-opioid pathway may have a pivotal intermediary role in the regulation of GnRH pulsatility

Gonadotropin releasing hormone (GnRH) is secreted from the hypothalamus and stimulates gonadotropic cells in the anterior pituitary gland to release luteinizing hormone and follicle-stimulating hormone, which in turn regulate the gametogenic and steroidogenic functions of the gonads in male and female.GnRH analog/r-hFSH therapy and IVF are two test which should be followed by women in the poor perfomance of GnRH.