Interactions between luteinizing hormone releasing hormone (LHRH), opioid receptors and estrogen in SK-N-SH human neuroblastoma cells

The purpose of this doctoral research project is to characterize the interactions between luteinizing hormone-releasing hormone (LHRH), opioid receptors and estrogen in SK-N-SH human neuroblastoma cells. LHRH, a decapeptide, also known as gonadotropin-releasing hormone, is produced by neurosecretory neurons in the brain. LHRH has been known to modulate the function of opioid receptors in neurons. Opioid agonists inhibit, while opioid antagonists stimulate gonadotropin release. The expression and release of LHRH is also regulated by estrogen.; SK-N-SH human neuroblastoma cells express mu (μ) and delta (δ) opioid receptors and respond to morphine. Culturing neuroblastoma cells in the presence of a differentiating agent such as all-trans-retinoic acid (RA) results in morphological conversions of the cells into a neuronal phenotype. Since SK-N-SH cells respond to RA, opioids, and express LHRH, the non-opiate neuropeptide, this cell line provides a useful in vitro model to study interaction of opioid, LHRH, and estrogen at the neuronal level.; Morphine caused reduction in LHRH levels in undifferentiated and differentiated cells, and the effect was dose and time-dependent. The effect of morphine was not prevented by the antagonist naloxone. Study with selective μ and δ opioid receptors agonist and antagonist showed that the morphine effect was mediated through δ opioid receptors.; Estrogen caused reduction in LHRH levels in undifferentiated and differentiated SK-N-SH cells. Tamoxifen (selective estogen receptor modulator) had antiestrogenic and estrogenic effect in SK-N-SH cells. The existence of an estrogen receptor β-like protein supports the notion that estrogen reduces LHRH levels in SK-N-SH cells through interaction with ERβ-like protein.; LHRH did not cause any significant changes in cyclic adenosine monophosphate (cAMP) at any dose and time. LHRH seems not to affect the function of opioid receptors through cAMP. The effects of LHRH on opioid receptors may involve other intracellular systems or receptors that are present in the SK-N-SH cells.