Desensitization of Pituitary Cells by Gonadotrophin-Releasing Hormone or its Analogues in the Superfusion System: Different Pattern for Males and Females

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Abstract
The effect of a 6-h infusion of gonadotrophin-releasing hormone (GnRH) or its analogues on dispersed anterior pituitary cells from male or female rats was investigated. The cells were stimulated with 3-min pulses of K(+) and GnRH. Thereafter GnRH (1 nM) or GnRH analogues ([D-Trp(6) ]GnRH-ethylamide ([D-Trp(6) ]GnRH, 50 pM), [D-Phe(6) , Gln(8) ]GnRH-ethylamide (Folligen, 100 pM) and [Asu(6) ]GnRH-ethylamide ([Asu(6) ]GnRH, 33 pM)) were applied for 6 h. In cells from female rats this treatment resulted in a 20-fold increase in luteinizing hormone (LH) secretion during the first 90-min period of the 6-h incubation. Following this a gradual decrease in LH release occurred, and during the fourth 90-min period the amount of LH secreted was only one-third or less of the initial value. The pituitary cells of male rats responded to the same treatment with only a 7-fold rise of LH secretion during the first period. In the second 90-min of the 6-h incubation a 20% to 30% increase was observed. Even in the fourth 90-min period the amount of LH secreted was two-thirds or more greater than that of the first 90-min period. When using 10-fold greater concentrations of the same peptides in males, the increase in hormone secretion in the second 90-min was not seen and the hormone release decreased to around 50%. We found definite differences in the responses of male and female rat pituitary cells to the 6-h infusion of GnRH or its analogues: the initial amplitude of the response in females was higher but desensitization was stronger. In males, the initial response was weaker; however, even using doses one magnitude greater, the level of desensitization did not reach the values obtained in females. The results were similar both with GnRH and the analogues. The responses to 3-min K(+) and GnRH stimuli given after the 6-h incubation were strongly reduced in cells from female rats compared to the initial responses; however, in cells from male rats the reaction was higher or unchanged. The ratio of LH released by the final K(+) stimulus relative to the actual LH content of the cells decreased in females but increased in males. Our data show that the differences between the pattern of desensitization in cells from male and female rats may be caused by the differences in the amount and ratio of immediately releasable hormone and the hormone replenishment into these pools.