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There are several lines of evidence that point to peptides participating in the regulation of LH and/or FSH levels by action at the pituitary. This evidence includes altered secretion of gonadotropins from the anterior pituitary cells or tissue in vitro when exposed to the peptide. Additionally, modification of GnRH-stimulated LH/FSH secretion has been observed. Furthermore, there is potential for a separately modulated interaction with the primed response. Another potential of action is by interaction among non-GnRH peptides on gonadotropin-regulating processes, although there are no good data available on this aspect. Other observations, consistent with a pituitary role for the peptides in modulation of LH, include detection of the peptides in portal blood, detection of high-affinity receptors or receptor mRNA in the pituitary, and detection of intrapituitary peptide or peptide mRNA in the pituitary. The modulation by steroids of both concentrations and type of activities provides a further level of physiological refinement. There is, however, some confusion regarding the involvement of these peptides in gonadotropin control. The reasons can be seen by considering aspects of investigations. There are experimental variations such as 1) species studied, e.g., NPY has been reported to have an effect on LH secretion from rat cells (168) but not on sheep anterior pituitary tissue (64), and substance P inhibits GnRH-stimulated release from rat cells (182) but potentiates the response in prepubertal porcine cells (92); 2) the steroidal conditions under which the study is performed, e.g., NPY has opposite effects in certain endocrine environments, augmenting GnRH-stimulated LH release in proestrus-like conditions (168), and inhibiting in metestrus-like environment (66); 3) the type of cell preparation, e.g., responsiveness to substance P might depend on whether cells in overnight culture were in separated or clustered state (91); 4) the time course considered, e.g., oxytocin that might induce marked LH release from pituitary cells after a longer length of incubation than GnRH requires (68); 5) length of exposure to peptide, e.g., endothelin that augmented or inhibited GnRH-stimulated LH release (50); 6) In addition, it is possible that the traditional endpoint selected in such studies, namely, observation of gonadotropin secretion, is not necessarily the most important for these peptides (56, 81, 117). Unfortunately, at this stage a definitive answer to the question "What do the peptides actually do?" cannot be provided and we remain tantalized by the glimpses of potential roles. Perhaps in a few years an updated review will be able to include a more complete answer. It is necessary for the full understanding of LH control that not only the properties of the peptides in isolation be characterized but also their interactions.

Modulation of Gonadotropin Levels by Peptides Acting at the Anterior Pituitary Gland