Indomethacin treatment prevents prolactin-induced luteolysis in the rat

1987 ◽  
Vol 112 (2) ◽  
pp. 317-322 ◽  
Author(s):  
J. E. Sánchez-Criado ◽  
K. Ochiai ◽  
I. Rothchild

ABSTRACT Adult female rats were hypophysectomized and their pituitary glands autotransplanted beneath the left kidney capsule on day 2 (day 1 was the day of ovulation). In such rats the pituitary secretes prolactin fairly constantly and the corpora lutea secrete progesterone for several months. To induce the luteolytic effect of prolactin the rats were first injected s.c. with 2-bromo-α-ergocryptine (CB-154) on cycle days 12, 13 and 14 (i.e. 10, 11 and 12 days after operation) to depress prolactin secretion, and then with CB-154 vehicle (70% ethanol) daily until cycle day 21, to allow prolactin secretion to resume. One ovary was removed from each rat on day 15 and the remaining one on day 22. The mean (± s.e.m.) weight of the corpora lutea on day 15 was 1·46±0·06 mg and 0·98±0·07 mg on day 22 (n = 17). In contrast, rats in which the CB-154 treatment was maintained to day 21 had corpora lutea which weighed 1·31 ±0·09 on day 15 and 1·47 ±0·08 mg on day 22 (n = 15). To investigate whether indomethacin, a prostaglandin synthesis inhibitor, affected the luteolytic action of prolactin, the experiment was repeated, but on day 15 (after the removal of one ovary) the groups in which CB-154 treatment was stopped, as well as the group in which CB-154 treatment was maintained, were each divided into two groups. In one, indomethacin-containing silicone elastomer wafers and, in the other, blank silicone elastomer wafers, were placed within the bursa of the remaining ovary. There were no differences in corpus luteum weight on day 15 among any of these groups and the two groups of the first experiment. There was no significant difference in corpus luteum weight between day 15 and day 22 in any of the six groups except for the two groups treated with the CB-154 vehicle and not with indomethacin. Thus, treatment with indomethacin prevented the fall in corpus luteum weight associated with the discontinuation of CB-154 treatment. Serum prolactin levels fell until day 15 in all rats and remained low in those in which the CB-154 treatment was maintained to day 21, but returned to control values in those treated with vehicle after day 14. Serum progesterone levels fell and remained low in all groups. Indomethacin treatment had no effect on the levels of either serum prolactin or progesterone. We conclude that some of the pharmacological effects of indomethacin are to prevent prolactin-induced luteolysis, and we suggest that prolactin induces rapid regression of the corpus luteum by stimulating intraluteal prostaglandin production or by being necessary for the effect of luteolytic prostaglandins. J. Endocr. (1987) 112, 317–322

1976 ◽  
Vol 71 (1) ◽  
pp. 115-120 ◽  
Author(s):  
HIROSHI NAGASAWA ◽  
REIKO YANAI ◽  
KOREHITO YAMANOUCHI

SUMMARY Intact female rats given twice daily injections of 1 mg human placental lactogen (HPL) showed continued dioestrous vaginal smears and their ovarian corpora lutea were found to be hypertrophied and functional. The serum prolactin level was significantly lower in these rats than in the controls at dioestrus as well as at pro-oestrus. Twice-daily injections of 0·5 or 2 mg HPL to ovariectomized rats decreased serum and pituitary levels of prolactin and increased hypothalamic activity of prolactin inhibiting hormone, although the effect was less at the lower dose. Human placental lactogen had no direct effect on pituitary prolactin secretion in vitro. These findings have demonstrated that HPL, like prolactin itself, inhibits prolactin secretion by acting indirectly on the pituitary through the hypothalamus.


1996 ◽  
Vol 76 (3) ◽  
pp. 463-464 ◽  
Author(s):  
W. A. Cerbito ◽  
M. P. B. Wijayagunawardane ◽  
M. Takagi ◽  
K. Sato ◽  
A. Miyamoto ◽  
...  

Bovine uterine horns with both ovaries containing a corpus luteum (CL) were compared for progesterone (P4) and oxytocin (OT) concentrations during the luteal phase of the estrous cycle. Uterine tissue samples from five Holstein cows with bilateral CL obtained from the slaughterhouse were used for this study. No significant difference was observed in P4 and OT levels in the right and left horns with corpora lutea in both ovaries. The data clearly indicate that both sides of the uterine horn having a functional CL are exposed to similar levels of P4 and OT, supporting the hypothesis that luteal products are delivered locally to the uterus. Key words: Progesterone, oxytocin, uterine horn, bilateral, corpus luteum, cow


1995 ◽  
Vol 145 (3) ◽  
pp. 449-454 ◽  
Author(s):  
J Th J Uilenbroek ◽  
P van der Schoot ◽  
J A M Mattheij ◽  
J J M Swarts

Abstract To study the effects of the antiprogestagen RU486 on luteal activity in pseudopregnant rats, adult female rats made pseudopregnant by sterile copulation were given daily injections with oil vehicle or with RU486 (2 mg/day) either during the entire period of pseudopregnancy (day 1 till day 14) or during the second half of pseudopregnancy (day 8 till day 14). Blood was taken every other day to measure serum concentrations of progesterone. At autopsy, on day 15, the weights of ovaries, isolated corpora lutea and pituitary glands were recorded. In a second study using the same experimental protocol, blood was taken via a jugular vein cannula on days 8, 9, 10 and 11 after induction of pseudopregnancy; on each of these days blood samples were taken at 0700, 0800 and 0900 h, and at 1700, 1800 and 1900 h to measure plasma concentrations of prolactin, LH and progesterone. Administration of RU486 from day 1 of pseudopregnancy onwards had no effect on the increasing concentrations of serum progesterone during the first half of pseudopregnancy. Thereafter progesterone concentrations increased further in RU486-treated rats whereas they decreased in oil-treated pseudopregnant rats. Administration of RU486 from day 8 of pseudopregnancy onwards resulted in a decline in progesterone concentrations in serum on day 10 followed by ovulation on day 11. Plasma LH concentrations in rats treated with RU486 from day 1 of pseudopregnancy were higher than those in oil-treated rats on days 8, 9, 10 and 11. Treatment from day 8 of pseudopregnancy resulted in low LH concentrations at days 8 and 9 and the presence of a preovulatory surge of LH on the afternoon of day 10 (day of pro-oestrus). Plasma concentrations of prolactin measured in oil-treated rats showed two daily surges of similar magnitude in the morning and afternoon of days 8, 9, 10 and 11. In animals treated with RU486 from day 8 onwards, the afternoon surge on day 9 and the morning surge on day 10 were absent. This demonstrated that the luteolytic effect of RU486 when given during the second part of pseudopregnancy is due to a blockade in the afternoon surge of prolactin on day 9. In animals treated with RU486 from day 1 of pseudopregnancy onwards, prolactin in the early morning samples was low, while prolactin in the afternoon samples was highly elevated. At autopsy on day 15, the weights of ovaries, corpora lutea and pituitary glands in animals treated with RU486 from day 1 were larger than those in oil-treated rats; this is in line with an increased secretion of prolactin. In contrast, in animals treated with RU486 from day 8, pituitary weight was not elevated and the increase in ovarian weight was due to the presence of two generations of corpora lutea. In conclusion, whether or not RU486 is luteolytic in pseudopregnant rats depends on the time of administration: injection during the second half of pseudopregnancy inhibits prolactin secretion and induces luteolysis, while administration during the early phase of pseudopregnancy results in high concentrations of prolactin in the early afternoon and therefore prevents luteolysis. Journal of Endocrinology (1995) 145, 449–454


1975 ◽  
Vol 55 (4) ◽  
pp. 633-640 ◽  
Author(s):  
J. G. MANNS ◽  
H. D. HAFS ◽  
G. E. LAMMING

Four Friesian heifers 14–16 mo of age were injected through jugular catheters six times per day (0600, 0900, 1200, 1500, 1800 and 2100 h) with 100 μg thyrotropin-releasing hormone or saline (control). TRH and saline treatment continued for 14 days beginning 1 day after a luteolytic dose of prostaglandin (PGF2α, 30 mg) which was given during diestrus. Blood samples were collected via the catheters at 0900 and 2100 h each day for progesterone prolactin and LH determinations and before and 10, 20, 30, 40 and 60 min after the 0600 and 2100 h TRH injections on the 1st, 7th and 13th days of treatment for growth hormone (GH) and prolactin analysis. After 14 days, heifers were injected with 10 mg PGF2α and changes in blood progesterone were measured for 24 h. There were two treatment periods; hence, each animal was subjected to both TRH and saline injections. Results support the following conclusions: (1) Prolactin secretion in response to TRH did not diminish with time. (2) Plasma progesterone of TRH-treated animals was lower (P < 0.05) from approximately day 5 of the cycle (estrus = day 0) until corpora lutea were destroyed with PGF2α; this provides no support for a luteotrophic role for prolactin. (3) Corpora lutea of all animals regressed after 10 mg PGF2α, suggesting that TRH had not increased the resistance of the corpus luteum to the luteolytic effects of PGF2α.


2021 ◽  
Vol 10 (6) ◽  
pp. e5110615536
Author(s):  
Leonardo Augusto Lombardi ◽  
Leandro Sabará Mattos ◽  
Marcio Luis Alves Moura ◽  
Ana Paula Espindula ◽  
Ricardo Santos Simões ◽  
...  

Objective: To evaluate the histomorphometric and immunohistochemical changes in interstitial cells and ovarian follicles of rats treated with metformin during and after induction of permanent estrus. Methods: Thirty-two adult-female rats with regular estrous cycle were equally divided into four groups: 1) GCtrl - at estrous phase. 2) GPCOS - at permanent-estrous phase. 3) GMet1 - rats and daily treated with metformin (12.5 mg/Kg) during 60 consecutive days, as preventive form and 4) GMet2 - PCOS rats, which remained exposed to 60 days of continuous illumination and treated with metformin. After that, the animals were euthanized, and the ovaries were removed and processed for paraffin embedding. Sections were stained with H.E. for histomorphometry or subjected to immunohistochemistry for Ki-67 and cleaved caspase-3 (Casp-3) detections. Results: The GPCOS showed lack of corpus luteum and several ovarian cysts, as well as interstitial-like cells. The presence of corpus luteum and a significant increase in primary and antral follicles were observed in Mel-treated groups, which also showed a decrease in the number of ovarian cysts and in the area occupied by interstitial-like cells. The presence of corpus luteum along with an increase in the number of primary follicles in the Met2 group were noticed (p<0,01). A significant reduction in number of cysts and in the area occupied by interstitial cells, as well as a decrease in nuclear volume of interstitial cells, were noticed in the Met-treated groups, mainly in the Met2 group. The percentage of cell proliferation was significantly higher in granulosa cells of the Met-treated groups than PCOS group, mainly in the GMet2 (p<0,01), which was similar to the GCtrl group. On the other hand, the percentage of apoptosis (cleaved-caspase-3- positive cells) was significantly higher in the granulosa cells of GPCOS and Met-treated groups than the GCtrl group, but without significant difference, which showed weak cleaved caspase-3 immunoreactivity in those cells. Conclusion: The ovaries of rats treated with metformin showed a decrease in nuclear volume and in the area occupied by interstitial cells, presence of corpus luteum, in addition to a decrease in the number of cysts.


1987 ◽  
Vol 115 (3) ◽  
pp. 387-393
Author(s):  
B. Eckstein ◽  
I. Khan ◽  
G. Gibori

ABSTRACT The purpose of this study was to assess the substrate specificity of P45017α in both the corpus luteum and placenta of pregnant rats, and to analyse the site at which LH/human chorionic gonadotrophin (hCG) regulates the activities of this enzyme. To distinguish the substrate preference, placentas and corpora lutea were obtained from rats on day 15 of pregnancy. Tissues were homogenized and the 10 000 g supernatants incubated in the presence of equimolar concentrations of [14C]progesterone and [3H]17α-hydroxyprogesterone as substrate with either NADH or NADPH as cofactors for 2, 8, 16 and 24 min. The labelling pattern of both 17α-hydroxyprogesterone and testosterone indicated that the corpus luteum produced testosterone preferentially from progesterone, whereas the placenta principally used 17α-hydroxyprogesterone and synthesized six times as much testosterone from 17α-hydroxyprogesterone than from progesterone. Addition of either NADPH or NADH as cofactors had no effect on substrate preference. The products of the two enzymatic activities were identified by recrystallization to constant 14C/3H ratios. The ratio of 14C/3H in testosterone produced by the corpus luteum was 16-fold higher than in that produced by the placenta. To explore which of the two activities of P45017α is regulated by the gonadotrophin, rats were treated with either 1·5 IU hCG or vehicle between days 13 and 15 of pregnancy. Hydroxylase and lyase activities were determined on day 15 after incubation for 2,8,16 or 24 min in the presence of either NADH or NADPH. Administration of hCG significantly inhibited NADH-dependent 17α-hydroxylase in the placenta at each time-point studied. The inhibition reached 69% at 24 min. Human chorionic gonadotrophin did not affect the NADPH-dependent 17α-hydroxylase and had only a slight inhibitory effect on both NADH- and NADPH-dependent 17,20-lyase activities in the placenta. In contrast to its effect on the placenta, hCG stimulated both NADH- and NADPH-linked 17,20-lyase activities but had no measurable effect on 17α-hydroxylase activities in the corpus luteum. In summary, the results of the present investigation have revealed a significant difference in the behaviour of 17α-hydroxylase/17,20-lyase activities in the placenta and corpus luteum. The substrate preference and the control of both enzyme activities by LH/hCG differs dramatically. J. Endocr. (1987) 115, 387–393


1988 ◽  
Vol 16 (01n02) ◽  
pp. 11-19 ◽  
Author(s):  
Satoshi Usuki

27-day-old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were perifused with NIH-LH, Tokishakuyakusan (TJ-23) or its components. LH and TJ-23 increased progesterone in media and LH was more effective than TJ-23. Hoelen, Peony root, Alisma rhizome and Japanese angelica root also agumented progesterone. 17α-hydroxyprogesterone and 20 α-hydroxyprogesterone were not stimulated by TJ-23. These results suggest that TJ-23 stimulates corpora lutea to secrete progesterone without direct luteotropic or luteolytic effect and that the effect may be attributable to Hoelen, Peony root, Alisma rhizome or Japanese angelica root.


2001 ◽  
Vol 280 (3) ◽  
pp. R705-R712 ◽  
Author(s):  
Kun-Ruey Shieh ◽  
Jenn-Tser Pan

Effects of orphanin FQ (OFQ) on central dopaminergic (DA) neurons and serum prolactin (PRL) were examined in ovariectomized, estrogen-primed Sprague-Dawley rats. The activities of central DA neurons, including the tuberoinfundibular (TI), nigrostriatal, mesolimbic, and incertohypothalamic ones, were determined by measuring the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), the major metabolite of dopamine, in their projection regions in the brain by HPLC plus electrochemical detection. Intracerebroventricular administration of OFQ lowered DOPAC levels in the median eminence (ME), striatum, nucleus accumbens, and hypothalamic paraventricular nucleus in a dose (0.01–10 μg)- and time (30–90 min)-dependent manner. In contrast, OFQ increased DOPAC in the suprachiasmatic nucleus and had no effect in the periventricular nucleus. Serum PRL levels exhibited a typical inverse relationship with the activity of TIDA neurons, as determined by DOPAC levels in the ME. In the afternoon, we observed an endogenous decrease of ME DOPAC level accompanied by a PRL surge in estrogen-primed female rats. Although OFQ caused further decrease of ME DOPAC in the afternoon, it failed to augment the PRL surge level. Although pretreatment of an antisense oligodeoxynucleotide against the opioid receptor-like receptor gene had no effect on basal ME DOPAC levels in the morning or afternoon, it attenuated the afternoon PRL surge. Furthermore, it blocked the effects of exogenous OFQ on ME DOPAC and serum PRL levels, whereas the sense or missense oligodeoxynucleotide had no effect. These results indicate that OFQ and its receptors may be involved in the regulation of central DA neuronal activity and PRL secretion.


1963 ◽  
Vol 43 (2) ◽  
pp. 246-254 ◽  
Author(s):  
G. H. Zeilmaker

ABSTRACT The functional activity of artificially induced corpora lutea in isologous ovaries transplanted into castrated male rats has been studied. Criteria for progesterone production were the morphology of vaginal transplants and the distribution of sudanophilic material in the corpus luteum cells. It was found that spontaneous functional activity of the corpora lutea did not occur in short-term experiments. Progesterone production was observed, however, in animals also bearing an isotransplanted (either male or female) pituitary gland, and in animals which received daily injections of reserpine. It is suggested that the normal influence of the central nervous system on the secretion of luteotrophic hormone is inhibitory in male as well as in female animals. Some aspects of the induction and maintenance of luteal function in castrated male rats bearing a transplanted ovary have been studied and compared with similar phenomena in the female rat. A real pseudopregnancy, i. e. maintained by the pituitary in situ during a defined period, as can be observed in female rats, could not be induced in these animals. In animals also bearing an isografted pituitary gland, luteolysis was not observed in experiments lasting up to 45 days. It is suggested that these findings may be correlated with the way in which the luteinizing hormone is secreted in the male rat.


1991 ◽  
Vol 19 (01) ◽  
pp. 57-60 ◽  
Author(s):  
Satoshi Usuki

Twenty-seven-day old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were incubated in vitro with herbal components of Tokishakuyakusan (TS). Mixture of hoelen + peony root + alisma rhizone + Japanese angelica root or hoelen + Japanese angelica root or Japanese angelica root + cnidium rhizome significantly increased progesterone secretion, and these levels tended to exceed the level by TS alone. These results suggest an exquisitely blended effect of herbal components of TS on progesterone secretion by corpora lutea.


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