Chronic exposure of the developing corpus luteum in monkeys to chorionic gonadotropin

Persistent progesterone production despite desensitization of adenylate cyclase

C. A. Vandevoort, R. L. Stouffer, T. A. Molskness, J. S. Ottobre

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The transient steroidogenic response of the macaque corpus luteum to chronic human CH (hCG) treatment beginning on days 9-10 of the luteal phase (i.e. stimulated early pregnancy) is associated with decreased numbers and affinity of available receptors for gonadotropin and homologous desensitization of adenylate cyclase. This study determined if similar changes in the receptor-adenylate cyclase system accompany the persistent steroidogenic response which occurs when hCG treatment begins earlier in the luteal phase. Female rhesus monkeys received increasing doses of hCG (15 up to 5760 LU) twice daily beginning 5-6 days after the midcycle LH surge. The levels of circulating progesterone increased (P < 0.05) within 24 h of initial hCG exposure and did not decrease throughout the 10-day regimen. The corpus luteum was removed after 0 (n = 8), 6 (n = 4), or 10 (n = 4) days of hCG treatment. Whereas the numbers of available [125I]hCG binding sites in luteal particulates remained unchanged by 10 days of hCG exposure, the dissociation constant (K(d)) for gonadotropin binding was greater than at day 0 (6.17 ± 1.41 vs. 0.91 ± 0.06 x 10-10 M, P < 0.05). Since the number of binding sites occupied by injected hCG increased with treatment (7.81 ± 1.55 fmol/mg wet wt at day 10), the total number (available + occupied) of gonadotropin receptors was 3-fold greater (P < 0.05) at day 10 than at day 0. Adenylate cyclase activity in luteal homogenates, assessed by conversion of [α-32P]ATP to [32P]cAMP, was stimulated on day 0 by hCG (2.7 ± 0.7 x control, at 250 nM hCG), prostaglandin E2 (2.5 + 0.5 x control, at 0.5 mM), and prostaglandin I2 (2.3 ± 0.5 x control at 0.5 mM) as well as forskolin (100 μM) and 5'-guanylyl-imidodiphosphate (50 μM). In contrast, cAMP production by day 6 of treatment was insensitive to hCG, but remained responsive to prostaglandin E2, prostaglandin I2, and nonhormonal activators. We conclude that CG treatment in the early luteal phase did not prevent the development of gonadotropin receptors to levels typically observed in the functional corpus luteum of the menstrual cycle. Also, many changes in the gonadotropin receptor-adenylate cyclase system in macaque luteal tissue were similar after CG treatment beginning on days 5-6 or days 9-10 of the luteal phase. Thus, these membrane events may not mediate the transitory response of the primate corpus luteum to CG in early pregnancy; indeed, luteal steroidogenesis can persist despite desensitization of adenylate cyclase to gonadotropin.

Original languageEnglish (US)
Pages (from-to)1876-1882
Number of pages7
JournalEndocrinology
Volume122
Issue number5
StatePublished - 1988

Fingerprint

Corpus Luteum
Chorionic Gonadotropin
Adenylyl Cyclases
Haplorhini
Progesterone
Gonadotropin Receptors
Luteal Phase
Macaca
Epoprostenol
Gonadotropins
Dinoprostone
Binding Sites
Guanylyl Imidodiphosphate
Pregnancy
Colforsin
Menstrual Cycle
Macaca mulatta
Primates
Adenosine Triphosphate
Membranes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Chronic exposure of the developing corpus luteum in monkeys to chorionic gonadotropin : Persistent progesterone production despite desensitization of adenylate cyclase. / Vandevoort, C. A.; Stouffer, R. L.; Molskness, T. A.; Ottobre, J. S.

In: Endocrinology, Vol. 122, No. 5, 1988, p. 1876-1882.

Research output: Contribution to journalArticle

Vandevoort, C. A. ; Stouffer, R. L. ; Molskness, T. A. ; Ottobre, J. S. / Chronic exposure of the developing corpus luteum in monkeys to chorionic gonadotropin : Persistent progesterone production despite desensitization of adenylate cyclase. In: Endocrinology. 1988 ; Vol. 122, No. 5. pp. 1876-1882.
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N2 - The transient steroidogenic response of the macaque corpus luteum to chronic human CH (hCG) treatment beginning on days 9-10 of the luteal phase (i.e. stimulated early pregnancy) is associated with decreased numbers and affinity of available receptors for gonadotropin and homologous desensitization of adenylate cyclase. This study determined if similar changes in the receptor-adenylate cyclase system accompany the persistent steroidogenic response which occurs when hCG treatment begins earlier in the luteal phase. Female rhesus monkeys received increasing doses of hCG (15 up to 5760 LU) twice daily beginning 5-6 days after the midcycle LH surge. The levels of circulating progesterone increased (P < 0.05) within 24 h of initial hCG exposure and did not decrease throughout the 10-day regimen. The corpus luteum was removed after 0 (n = 8), 6 (n = 4), or 10 (n = 4) days of hCG treatment. Whereas the numbers of available [125I]hCG binding sites in luteal particulates remained unchanged by 10 days of hCG exposure, the dissociation constant (K(d)) for gonadotropin binding was greater than at day 0 (6.17 ± 1.41 vs. 0.91 ± 0.06 x 10-10 M, P < 0.05). Since the number of binding sites occupied by injected hCG increased with treatment (7.81 ± 1.55 fmol/mg wet wt at day 10), the total number (available + occupied) of gonadotropin receptors was 3-fold greater (P < 0.05) at day 10 than at day 0. Adenylate cyclase activity in luteal homogenates, assessed by conversion of [α-32P]ATP to [32P]cAMP, was stimulated on day 0 by hCG (2.7 ± 0.7 x control, at 250 nM hCG), prostaglandin E2 (2.5 + 0.5 x control, at 0.5 mM), and prostaglandin I2 (2.3 ± 0.5 x control at 0.5 mM) as well as forskolin (100 μM) and 5'-guanylyl-imidodiphosphate (50 μM). In contrast, cAMP production by day 6 of treatment was insensitive to hCG, but remained responsive to prostaglandin E2, prostaglandin I2, and nonhormonal activators. We conclude that CG treatment in the early luteal phase did not prevent the development of gonadotropin receptors to levels typically observed in the functional corpus luteum of the menstrual cycle. Also, many changes in the gonadotropin receptor-adenylate cyclase system in macaque luteal tissue were similar after CG treatment beginning on days 5-6 or days 9-10 of the luteal phase. Thus, these membrane events may not mediate the transitory response of the primate corpus luteum to CG in early pregnancy; indeed, luteal steroidogenesis can persist despite desensitization of adenylate cyclase to gonadotropin.

AB - The transient steroidogenic response of the macaque corpus luteum to chronic human CH (hCG) treatment beginning on days 9-10 of the luteal phase (i.e. stimulated early pregnancy) is associated with decreased numbers and affinity of available receptors for gonadotropin and homologous desensitization of adenylate cyclase. This study determined if similar changes in the receptor-adenylate cyclase system accompany the persistent steroidogenic response which occurs when hCG treatment begins earlier in the luteal phase. Female rhesus monkeys received increasing doses of hCG (15 up to 5760 LU) twice daily beginning 5-6 days after the midcycle LH surge. The levels of circulating progesterone increased (P < 0.05) within 24 h of initial hCG exposure and did not decrease throughout the 10-day regimen. The corpus luteum was removed after 0 (n = 8), 6 (n = 4), or 10 (n = 4) days of hCG treatment. Whereas the numbers of available [125I]hCG binding sites in luteal particulates remained unchanged by 10 days of hCG exposure, the dissociation constant (K(d)) for gonadotropin binding was greater than at day 0 (6.17 ± 1.41 vs. 0.91 ± 0.06 x 10-10 M, P < 0.05). Since the number of binding sites occupied by injected hCG increased with treatment (7.81 ± 1.55 fmol/mg wet wt at day 10), the total number (available + occupied) of gonadotropin receptors was 3-fold greater (P < 0.05) at day 10 than at day 0. Adenylate cyclase activity in luteal homogenates, assessed by conversion of [α-32P]ATP to [32P]cAMP, was stimulated on day 0 by hCG (2.7 ± 0.7 x control, at 250 nM hCG), prostaglandin E2 (2.5 + 0.5 x control, at 0.5 mM), and prostaglandin I2 (2.3 ± 0.5 x control at 0.5 mM) as well as forskolin (100 μM) and 5'-guanylyl-imidodiphosphate (50 μM). In contrast, cAMP production by day 6 of treatment was insensitive to hCG, but remained responsive to prostaglandin E2, prostaglandin I2, and nonhormonal activators. We conclude that CG treatment in the early luteal phase did not prevent the development of gonadotropin receptors to levels typically observed in the functional corpus luteum of the menstrual cycle. Also, many changes in the gonadotropin receptor-adenylate cyclase system in macaque luteal tissue were similar after CG treatment beginning on days 5-6 or days 9-10 of the luteal phase. Thus, these membrane events may not mediate the transitory response of the primate corpus luteum to CG in early pregnancy; indeed, luteal steroidogenesis can persist despite desensitization of adenylate cyclase to gonadotropin.

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