Long-term effects of a gonadotrophin-releasing hormone agonist ([d-Ser(But)6]GnRH(1–9)nonapeptide-ethylamide) on gonadotrophin secretion from human pituitary gonadotroph cell adenomas in vitro

Abstract

We have studied the effects of TRH and native gonadotrophin-releasing hormone (GnRH), and of a GnRH agonist (Buserelin; [D-Ser(But )6]GnRH(1-9) nonapeptide-ethylamide), on LH, FSH, alpha subunit and LH-beta subunit secretion from three human gonadotrophin-secreting pituitary adenomas in dispersed cell culture. During a 24 h study, treatment with 276 nmol TRH/l resulted in a significant (P less than 0.05) stimulated release of FSH and alpha subunit from all three adenomas, and LH from the two adenomas secreting detectable concentrations of this glycoprotein; treatment with 85 nmol GnRH/l significantly (P less than 0.05) stimulated the release of alpha subunit from all three, but FSH from only two and LH from only one adenoma. During a long-term 28-day study, basal FSH and alpha subunit concentrations were maintained, but secretion of LH, and LH-beta (detectable from one tumour only), declined with time from two of the three adenomas. Addition of Buserelin to the cultures resulted in the continuous (P less than 0.05) stimulation of alpha subunit secretion from all three adenomas, and of LH and FSH from two, whilst a transient stimulatory effect on LH and FSH secretion was seen from a third adenoma, with subsequent secretion rates declining towards control values. These data show that human gonadotrophin-secreting adenomas demonstrate variable stimulatory responses to hypothalamic TRH and GnRH, and that during chronic treatment with a GnRH agonist the anticipated desensitizing effect of the drug was not observed in two out of the three adenomas studied. The mechanisms for this is not clear, but such drugs are unlikely to be of therapeutic value in the management of gonadotrophin-secreting tumours. The data also suggest that GnRH and GnRH agonists have a differential effect on the in-vitro release of intact gonadotrophins and the common alpha subunit.

Pituitary Microadenoma in Turner's Syndrome

“…However, the potential risks of cardiac surgery for these patients 11 may be relevant to Turner's syndrome with its associated congenital cardiac abnormalities. Treatment of gonadotroph cell adenoma with long‐acting agonists of gonadotrophin‐releasing hormone, with a view to suppression of the pituitary gonadal axis, has not shown conclusive benefits 12 . The addition of gonadal steroids has not shown any benefit 13…”

Gonadotrophin secretion in vitro by cells of a pituitary tumour from a patient with multiple endocrine neoplasia type I

“…After 2 days, medium from all the cultures was collected, pooled and centrifuged at 500 g for 5 minutes to remove detached cells and debris, and pituitary hormones were measured by radioimmunoassay as described previously (White et al, 1986). Long-term in-vitro maintenance of the pituitary tumour cells was essentially as reported earlier (Daniels et al, 1988), but when it became apparent that the cells were secretory, separate 24-hour medium collections were made from a group of six cultures at intervals between days 29 and 77 in uitro. These were stored at -20°C until assayed for gonadotrophins.…”

In vitro διεύρυνση της εκκριτικής δραστηριότητας των αδενωμάτων υπόφυσης

“…Τα γοναδοτρόπα αδενώματα ανταποκρίνονται με διαφορετικούς τρόπους στη διέγερση με GnRH ή με αγωνιστές της (Asa et al, 1988b, Lamberts et al, 1987b, Daniels et al, 1988. Μορφολειτουργικές συσχετί σεις έχουν δείξει ότι παρατεταμένη διέγερση με GnRH ευοδώνει την ορ μονική σύνθεση όπως και την έκκριση από τα κύτταρα γοναδοτρόπων αδενωμάτων (Asa et al, 1988b), γεγονός που τεκμηριώνεται από την αύ ξηση των επιπέδων των παραγόμενων ορμονών στο καλλιεργητικό μέσο αλλά και από την αυξημένη κυτταρική περιεκτικότητα σε γοναδοτροπίνες (Lamberts et al, 1987b).…”

“…Μορφολειτουργικές συσχετί σεις έχουν δείξει ότι παρατεταμένη διέγερση με GnRH ευοδώνει την ορ μονική σύνθεση όπως και την έκκριση από τα κύτταρα γοναδοτρόπων αδενωμάτων (Asa et al, 1988b), γεγονός που τεκμηριώνεται από την αύ ξηση των επιπέδων των παραγόμενων ορμονών στο καλλιεργητικό μέσο αλλά και από την αυξημένη κυτταρική περιεκτικότητα σε γοναδοτροπίνες (Lamberts et al, 1987b). Απευαισθητοποίηση των κυττάρων από την πα ρατεταμένη διέγερση με GnRH δεν παρατηρήθηκε (Daniels et al, 1988). Η παρατήρηση αυτή, που επίσης ισχύει για τους αντίστοιχους υποθαλαμικούς παράγοντες στα σωματότροπο και κορτικοτρόπα αδενώματα, υ ποδηλώνει ότι παρατεινόμενη διέγερση των αδενοϋποφυσιακών κυττά ρων από τον υποθάλαμο in vivo, δυνατόν να ενέχεται στην παθογένεση των αδενωμάτων.…”