Comparison of the luteolytic action of gonadotrophin-releasing hormone antagonist and cloprostenol, and the ability of human chorionic gonadotrophin and melatonin to override their luteolytic effects in the marmoset monkey

1991 ◽  
Vol 128 (1) ◽  
pp. 121-129 ◽  
Author(s):  
G. E. Webley ◽  
J. K. Hodges ◽  
A. Given ◽  
J. P. Hearn
Keyword(s):  
Corpus Luteum ◽  
Physiological Role ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Marmoset Monkey ◽  
Lhrh Antagonist ◽  
Gonadotrophin Releasing Hormone ◽  
Sites Of Action ◽  
Lh Secretion ◽  
Post Implantation

ABSTRACT The effects of the luteolytic and luteotrophic agents cloprostenol, human chorionic gonadotrophin (hCG) and melatonin on the corpus luteum have been investigated in marmoset monkeys treated with an LHRH antagonist to reduce endogenous LH secretion. This has allowed the effects of these agents to be investigated in the absence of the principal endogenous luteotrophin. Administration of the LHRH antagonist ([N-acetyl-dβNal1-d-pCl-Phe2-d-Phe3-d-Arg6-Phe7-Arg8-d-Ala10]NH2-LHRH) or cloprostenol between days 7 and 11 after ovulation (preimplantation) resulted in luteolysis. A significant (P<0·05) decrease in progesterone concentrations had occurred by 4 h after administration of the LHRH antagonist and was indeed preceded by a fall in LH concentrations. Coadministration of hCG with the LHRH antagonist prevented the fall in progesterone. In contrast, administration of cloprostenol resulted in an immediate fall in progesterone concentrations, to less than half the initial level within 1 h, and co-administration with hCG did not prevent the fall. Administration of hCG stimulated progesterone production when given 8 h after the LHRH antagonist but not after 24 h. Cloprostenol prevented the stimulation by hCG. Co-administration of melatonin with the LHRH antagonist did not prevent the decrease in progesterone concentrations. Melatonin was also not effective in preventing the fall in progesterone induced by cloprostenol. However, co-administration of melatonin and cloprostenol between days 17 and 21 after ovulation (post-implantation) significantly (P<0·05) delayed the fall in progesterone seen with cloprostenol alone. These results suggest that while the LHRH antagonist and cloprostenol have different sites of action their effect is similar at the corpus luteum, that is in depriving the corpus luteum of luteotrophic support. The results also suggest that melatonin may be able to influence the luteolytic action of cloprostenol but that its effect varies with the stage of the cycle. The physiological role for such an action, if any, remains unknown. Journal of Endocrinology (1991) 128, 121–129

Effects of a sustained release formulation of the gonadotrophin-releasing hormone agonist histrelin on serum concentrations of gonadotrophins and oestradiol, and ovarian LH/human chorionic gonadotrophin receptor content in the rat

1991 ◽  
Vol 131 (2) ◽  
pp. 211-218 ◽  
Author(s):  
J. W. Gunnet ◽  
K. T. Demarest ◽  
D. W. Hahn ◽  
E. Ericson ◽  
J. L. McGuire
Keyword(s):  
Pituitary Gland ◽  
Ovarian Function ◽  
Direct Action ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Release Formulation ◽  
Sustained Release Formulation ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion ◽  
Hcg Receptor

ABSTRACT Pituitary and ovarian function were studied during the loss and recovery of oestrous cyclical activity in rats following treatment with a sustained release formulation of the gonadotrophin-releasing hormone (GnRH) agonist [imidazole benzyl-d-His6,Pro9-ethylamide]-GnRH (histrelin). A single s.c. injection of microencapsulated histrelin (10–300 μg peptide/kg) induced a dose-dependent disruption of normal oestrous cyclical activity with a persistent dioestrous-like vaginal cytology. In preliminary studies, pituitary gland stimulation and desensitization were demonstrated when serum LH and FSH levels were greater 1 week after administration of 10 μg microencapsulated histrelin/kg compared with 300 μg microencapsulated histrelin/kg. Changes in pituitary and ovarian function were assessed over time following injection of microencapsulated histrelin (100 μg peptide/kg). LH secretion was maximal within 8 h and then gradually declined, remaining at dioestrous levels from days 7 to 28. Serum oestradiol concentrations remained low and rose above dioestrous levels only on day 28. In contrast, ovarian LH/human chorionic gonadotrophin (LH/hCG) receptor content fell within 8 h and, after a nadir on day 7, slowly returned to dioestrous levels by day 28. The increase in ovarian LH/hCG receptor content preceded any significant change in pituitary gonadotrophin secretion, indicating a differential pattern of recovery for pituitary and ovarian function. Subsequent studies tested the possibility that these temporal differences in pituitary and ovarian function may result from histrelin acting directly on these tissues. Treatment with histrelin microcapsules (300 μg peptide/kg) prevented any increase in LH secretion in response to a GnRH challenge 3 days later, indicating a direct action of histrelin on the pituitary gland. A direct action on the ovary was demonstrated by the ability of histrelin microcapsules (300 μg peptide/kg) to prevent stimulation of progesterone secretion by pregnant mare's serum gonadotrophin in hypophysectomized females. These studies indicated that, in the rat, histrelin can act simultaneously and independently on both the pituitary gland and the ovary. There are temporal differences in the pituitary and ovarian responses, with ovarian function recovering earlier than pituitary function. Journal of Endocrinology (1991) 131, 211–218

INHIBITION BY MELATONIN OF THE PITUITARY RESPONSE TO LUTEINIZING HORMONE RELEASING HORMONE IN VIVO

1978 ◽  
Vol 76 (3) ◽  
pp. 487-491 ◽  
Author(s):  
K. YAMASHITA ◽  
M. MIENO ◽  
T. SHIMIZU ◽  
ER. YAMASHITA
Keyword(s):  
Luteinizing Hormone ◽  
Carotid Artery ◽  
Anterior Pituitary ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Lh Rh ◽  
Lh Secretion

The rate of secretion of 17-oxosteroids by the testes of anaesthetized dogs in vivo was used as an index of LH secretion. Intracarotid injection of luteinizing hormone releasing hormone (LH-RH, 1, 5 or 10 μg/kg body wt) resulted in an increase in the testicular 17-oxosteroid secretion which was roughly proportional to the dose administered and which reached a maximum 60 min after the injection. Testicular output of 17-oxosteroids was unaffected by administration of melatonin (10 or 100 μg/kg body wt) into the carotid artery. When LH-RH (5 μg/kg) was injected into the carotid artery 3 h after intracarotid injection of melatonin (10 or 100 μg/kg), the testicular response to LH-RH was considerably diminished. Pretreatment with melatonin (100 μg/kg) did not alter the testicular response to human chorionic gonadotrophin (20 i.u./kg body wt) given i.v. It is concluded that melatonin may act directly on the anterior pituitary gland in dogs to inhibit the LH-RH-induced release of LH.

Oxytocin may play a role in the control of the human corpus luteum

1982 ◽  
Vol 95 (1) ◽  
pp. 65-70 ◽  
Author(s):  
G. J. S. Tan ◽  
R. Tweedale ◽  
J. S. G. Biggs
Keyword(s):  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Inhibitory Action ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Corpora Lutea ◽  
Luteal Cells ◽  
Progesterone Production ◽  
Human Corpus Luteum

The effects of oxytocin on dispersed luteal cells from human corpora lutea of the menstrual cycle were studied. Oxytocin at a concentration of 4 mi.u./ml produced a slight increase in basal progesterone production. However, higher oxytocin concentrations (400 and 800 mi.u./ml) markedly inhibited both basal and human chorionic gonadotrophin-induced progesterone production. These data provide evidence for an effect of oxytocin on the human corpus luteum. In view of the inhibitory action of oxytocin, increased secretion of this hormone may be important in the demise of the corpus luteum at the end of the menstrual cycle.

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