Induction of luteolysis by dihydrotestosterone in the pregnant rat

1981 ◽  
Vol 241 (6) ◽  
pp. E444-E448
Author(s):  
R. Sridaran ◽  
G. Gibori

A dihydrotestosterone (DHT) pellet (4 mg) inserted under each ovarian bursa on day 9 of pregnancy induced within 24 h, a 40% decline in serum progesterone (P) concentrations in rats; a further reduction was observed on days 12 and 15. Although P levels were significantly reduced by DHT treatment, fetuses remained alive on day 12. However, by day 15, complete abortion occurred in 75% of the rats, indicating that a decline in P secretion precedes abortion, To further determine whether the abortifacient action of DHT was due to its luteolytic effect, 20-cm DHT capsules were implanted subcutaneously in ovariectomized rats treated with 4 mg P and 0.5 micrograms of estradiol (E). Control rats were sham-operated and treated with empty capsules. DHT treatment induced complete abortion by day 15 only in rats with ovaries present, further indicating that DHT was not directly detrimental to the fetuses but acted on the ovaries to induce luteolysis. When DHT treatment was started on day 12, no luteolytic effect was detectable. To determine whether the effect of DHT was mediated by either a decrease in the ovarian production of E, a decline in luteal cell content of luteinizing hormone (LH) receptors or both, testosterone (T) levels in the peripheral circulation and E and P concentrations in the ovarian vein were measured on day 15 in rats implanted with two DHT pellets under the ovarian bursa on day 9. Luteal content of LH receptors was also measured on day 12 in similarly treated rats. DHT treatment had no effect on serum levels or on ovarian vein concentration of E, but induced a significant decrease in the ovarian vein levels of P. DHT also did not depress LH receptor content in corpora lutea. DHT levels in the ovaries increase significantly between days 18 and 22 of pregnancy, concomitant with the cessation of corpus luteum function. These results indicate that DHT possesses a potent luteolytic activity and could be involved in the luteolytic process in the pregnant rat.

Reproduction ◽  
2005 ◽  
Vol 129 (1) ◽  
pp. 61-73 ◽  
Author(s):  
T A Bramley ◽  
D Stirling ◽  
G S Menzies ◽  
D T Baird

Seasonally anoestrous Welsh Mountain ewes received 250 ng gonadotrophin-releasing hormone (GnRH) every 2 h, with (Group 1;n= 13) or without (Group 2;n= 14) progesterone priming for 48 h. Fourteen control ewes (Group 3) were studied during the luteal phase in the breeding season. Animals in Group 4 (n= 12) received progesterone priming followed by 250 ng GnRH at increasing frequency for 72 h, while ewes in Group 5 (n= 13) were given three bolus injections of 30 μg GnRH at 90-min intervals. All treatment regimens induced ovulation. However, only corpora lutea (CL) from ewes in Group 3 (breeding season) or Group 4 exhibited normal luteal function. Luteal luteinizing hormone (LH) receptor levels were significantly higher on day 12 than day 4, and CL from groups with adequate CL (3 and 4) had significantly higher125I-human chorionic gonadotrophin (hCG)-binding levels than the three groups with inadequate CL on day 12. LH-binding affinity was unchanged. Exogenous ovine LH (10 μg)in vivoon days 3 or 11 after ovulation induced a pulse of progesterone in ewes with adequate CL: however, ewes in Groups 1, 2 and 5 showed no significant response. Basal progesterone secretionin vitrowas significantly greater on day 4 than on day 12. Maximal steroidogenic responses of adequate and inadequate CL to hCG and to dibutyryl cyclic-3′,5′-AMP were similar at both stages of the luteal phase. However, the EC50for hCG on days 4 and 12 was 10-fold lower for groups with an adequate CL (0.1 IU hCG/ml) than for inadequate-CL groups (1 IU hCG/ml;P<0.05). Thus, in addition to the well-characterized premature sensitivity of GnRH-induced inadequate CL to endometrial luteolysin, we have shown (1) a marked decrease in total number of cells in the CL, a profound reduction in vascular surface area, and a decrease in mean large luteal cell volume (with no change in large luteal cell numbers), (2) decreased luteal LH receptor and progesterone content compared with adequate CL and (3) that CL that were becoming, or were destined to become, inadequate failed to respond to ovine LHin vivoand were 10-fold less sensitive to hCG in terms of luteal progesterone secretionin vitro.


Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 3942-3951 ◽  
Author(s):  
Araya Anupriwan ◽  
Matthias Schenk ◽  
Kessiri Kongmanas ◽  
Rapeepun Vanichviriyakit ◽  
Daniela Costa Santos ◽  
...  

Arylsulfatase A (AS-A) is a lysosomal enzyme, which catalyzes the desulfation of certain sulfogalactolipids, including sulfogalactosylglycerolipid (SGG), a molecule implicated in cell adhesion. In this report, immunocytochemistry revealed the selective presence of AS-A in the corpus luteum of mouse ovaries. Immunoblotting indicated that mouse corpus luteum AS-A had a molecular mass of 66 kDa, similar to AS-A of other tissues. Corpus luteum AS-A was active, capable of desulfating the artificial substrate, p-nitrocatechol sulfate, at the optimum pH of five. To understand further the role of AS-A in female reproduction, levels of AS-A were determined during corpus luteum development in pseudopregnant mice and during luteolysis after cessation of pseudopregnancy. Immunocytochemistry, immunoblotting and desulfation activity showed that AS-A expression was evident at the onset of pseudopregnancy in the newly formed corpora lutea, and its level increased steadily during gland development. The increase in the expression and activity of AS-A continued throughout luteolysis after the decrease in serum progesterone levels. We also observed the selective presence of SGG on the luteal cell surface in developed corpora lutea, as shown by immunofluorescence of mouse ovary sections as well as high-performance thin-layer chromatography of lipids isolated from mouse and pig corpora lutea. The identity of the “SGG” band on the thin layer silica plate was further validated by electrospray ionization mass spectrometry. Significantly, SGG disappeared in regressing corpora lutea. Therefore, lysosomal AS-A may be involved in cell-surface remodeling during luteolysis by desulfating SGG after its endocytosis and targeting to the lysosome.


1981 ◽  
Vol 90 (1) ◽  
pp. 9-18 ◽  
Author(s):  
P. F. TERRANOVA ◽  
G. S. GREENWALD

Pregnant rats were injected s.c. with antiserum to LH (anti-LH) on days 8 or 10 of pregnancy (day 1 = day of sperm-positive vaginal smear) and subsequently given various steroids s.c. to prevent luteolysis and/or abortion. A single injection of 4 mg progesterone on day 8 prevented abortion and luteolysis as shown on day 12 by the presence of fetal swellings and levels of progesterone in serum (88 ±6 (s.e.m.) ng/ml) and corpora lutea (26±3 ng/mg) comparable to control values. After 0·5 ml anti-LH on day 10, a daily dose of 4 mg progesterone prevented abortion in five out of eight animals but by day 13 luteal progesterone was 3·0 ± 0·7 compared with 24±3 ng/mg in controls. After anti-LH on day 8 or 10, daily injections of 1 or 4 mg testosterone propionate or 10 μg, 100 μg or 1 mg oestradiol failed to prevent abortion or to raise luteal concentrations of progesterone to normal values. However, 4 mg testosterone propionate on day 8 or 100 or 500 μg oestradiol on day 10 maintained serum progesterone levels at approximately half those of control values. Treatment with 4 mg testosterone propionate on days 8–11 led to significant increases in serum and luteal levels of testosterone and oestradiol on day 12; on day 10 exogenous oestradiol (100 or 500 μg) increased serum and luteal levels of oestradiol by day 13. These results, especially treatments begun on day 8, are difficult to reconcile with the current concept that the luteotrophic action of LH in the pregnant rat is exerted by increasing luteal androgens that are aromatized to oestrogens which then act as the direct luteotrophic stimulus.


1984 ◽  
Vol 247 (6) ◽  
pp. E808-E814
Author(s):  
K. C. Yuh ◽  
C. H. Bill ◽  
P. L. Keyes

The requirement of the pituitary gland and the role of 17 beta-estradiol in the early development of the corpus luteum was investigated in rabbits hypophysectomized the day after sterile mating (day 1). Serum progesterone in hypophysectomized rabbits was normal for 2 days after hypophysectomy. Luteal tissue from hypophysectomized and sham-hypophysectomized rabbits had similar wet weight (4.0 +/- 0.4 vs. 5.3 +/- 0.2 mg/corpus luteum) and similar concentrations of available cytoplasmic estrogen receptor (1.2 +/- 0.2 vs. 1.5 +/- 0.3 fmol/micrograms DNA) and luteinizing hormone (LH) receptor (4.0 +/- 0.2 vs. 6.1 +/- 1.4 fmol/micrograms DNA) on day 4 of pseudopregnancy. Serum progesterone in hypophysectomized rabbits began to decline on day 4 and was undetectable by day 6. Estrogen receptor and luteal weight in hypophysectomized animals also declined after day 4 to low values by day 6, and serum estradiol was undetectable. However, if estradiol was administered by Silastic capsule implanted subcutaneously at the time of hypophysectomy or 3 days after hypophysectomy, serum progesterone, luteal weight, estrogen receptor, and LH receptor were maintained on day 6 of pseudopregnancy. These results indicate that after a preovulatory gonadotropin surge, the function of newly formed corpora lutea is normal for 3–4 days in the absence of pituitary hormones. However, by 4 days after ovulation, estradiol is required to sustain the structural and functional integrity of corpora lutea.


1971 ◽  
Vol 68 (1_Supplb) ◽  
pp. S53
Author(s):  
H. Rajaniemi ◽  
T. Vanha-Perttula

1983 ◽  
Vol 98 (1) ◽  
pp. 7-17 ◽  
Author(s):  
R. F. Walker

In ovariectomized rats treated chronically with oestrogen there is a loss of positive feedback effects on LH secretion. This was not due to depletion of pituitary LH since injection of LH releasing hormone (LH-RH; 50 ng/100 g body wt) caused a significant (P < 0·01) rise in serum LH even after the loss of spontaneous LH surges. However, the magnitude of the increase in serum LH in response to LH-RH was greater (412 ± 41 μg/l) before than after (291 ± 29 μg/l) loss of the LH surges. Excessive blood sampling was also not responsible, since positive feedback responses declined comparably in rats bled daily or once every 3–4 days. Progesterone (0·5 mg s.c.), administered for 5 consecutive days, failed to restore LH surges indicating that deficiency of this steroid after ovariectomy does not cause positive feedback responses to disappear in rats exposed chronically to oestrogen. Moreover regular daily fluctuations in serum progesterone, probably of adrenal origin, occurred before as well as after daily LH surges were lost. Serotonin content and turnover were depressed (P < 0·05) when ovariectomized rats first received the subcutaneous capsules containing oestrogen. This change correlated temporally with the onset of daily LH surges and was eventually lost. After 30 days exposure to oestrogen, serotonin turnover increased (P < 0·01) and positive feedback responses were absent. Catecholamine levels and turnover did not show differential responses to oestrogen and were depressed after acute as well as chronic steroid treatment. p-Chlorophenylalanine (pCPA; 250 mg/kg)+ l-dihydroxyphenylalanine (l-DOPA; 200 mg/kg), which depress serotonin and enhance catecholamine synthesis respectively, failed to reinstate LH surges, but these were restored in 22% of the rats receiving l-DOPA alone. pCPA, followed 2 days later by 5-hydroxytryptophan (5-HTP) at 11.00 h, reinstated LH surges in 88% of rats, and a dose–response curve showed that as little as 4 mg 5-HTP/kg stimulated repetitive LH surges when given with pCPA according to this schedule. However, the administration of α-methyl-p-tyrosine + l-DOPA, an analogous treatment involving catecholamines, was only marginally effective (15%). These findings suggest that perturbations of monoamine metabolism occurring in ovariectomized rats exposed to oestrogen for several weeks contribute to loss of daily LH surges. Since pCPA + 5-HTP restored LH surges most effectively, then positive feedback may disappear as the facilitatory effect of serotonin is lost after chronic oestrogen administration.


1985 ◽  
Vol 106 (1) ◽  
pp. 37-42 ◽  
Author(s):  
C. Hiemke ◽  
B. Poetz ◽  
R. Ghraf

ABSTRACT Long-term (4–6 weeks) ovariectomized rats were injected with either oestradiol benzoate (OB; 20 μg s.c.) or monohydroxytamoxifen (MTAM; 0·2 mg i.p.) plus OB. Oestradiol benzoate was administered at 12.00 h on day 0 and MTAM was given immediately before OB, followed by further injections twice daily to maintain sufficiently high antioestrogen levels. When given alone, OB reduced the serum levels of LH during the morning (08.00–09.00 h) and afternoon (17.30–18.30 h) hours of day 3 after priming. The feedback actions of OB on LH release were accompanied by time-dependent alterations of noradrenaline turnover in the preoptic–anterior hypothalamic brain area (POAH). On day 3 after priming the noradrenaline turnover rate was reduced in the morning and increased in the afternoon. The increase correlated with an enhanced sensitivity of the LH secretory system to progesterone. The antioestrogen MTAM blocked the OB-induced sensitization of LH release to the stimulatory action of progesterone and interfered with the stimulatory long-term effect of oestradiol on hypothalamic noradrenaline turnover. The data strongly support the view that the oestrogen-induced afternoon increase of noradrenaline turnover in the POAH represents a pre-requisite for the induction of LH surges. The stimulatory effect of oestradiol on hypothalamic noradrenaline turnover seems to be mediated by a classical oestrogen receptor mechanism. J. Endocr. (1985) 106, 37–42


1983 ◽  
Vol 63 (2) ◽  
pp. 331-347 ◽  
Author(s):  
J. G. MANNS ◽  
W. D. HUMPHREY ◽  
P. F. FLOOD ◽  
R. J. MAPLETOFT ◽  
N. RAWLINGS ◽  
...  

Three experiments were conducted to evaluate endocrine profiles and to determine the morphological and functional characteristics of corpora lutea (CL) following the onset of postpartum ovarian activity in beef cows, suckled by a single calf once daily. In exp. 1, blood samples were collected from 12 cows at 6-h intervals beginning 25 days postpartum until ovariectomy which was carried out on each of two cows on days 25, 27, 29, 31, 33, 35 after parturition. Ovarian structures were examined grossly and histologically. In exp. 2, blood samples were collected from eight cows at 6-h intervals for 18 days beginning 25 days postpartum and at less frequent intervals thereafter. Laparotomies were carried out on day 36 after calving, the ovaries were observed, CL were sampled and the residual tissue was marked with charcoal. A second laparotomy was performed on day 50. Luteal tissue samples were processed and examined by light and electron microscopy. Luteal cell types were evaluated, percent of area covered by large cells was determined and average luteal cell diameter was calculated. In exp. 3, seven cows were bled daily from parturition until day 25 postpartum. Serum from all experiments was assayed for progesterone (P4), FSH, LH and a prostaglandin metabolite (PGFM). The data showed that serum PGFM levels declined from a peak at calving to basal levels by 10 days postpartum which was well before the first ovulation. In all instances the observed peaks of serum LH and serum FSH preceded the first rise in P4 which, in eight of nine cases, was due to a functional CL. These CL were functional for periods of time ranging from 3 to 12 days. The regression of short-lived CL appeared abnormal compared to the longer-lived CL in which regression was characterized by a rapid decline in P4 and elevated blood PGFM. These data show clearly that the first increase in P4 is preceded by a typical LH surge, followed by ovulation and CL formation which has a variable life-span. Key words: Beef cows, postpartum, anestrus, corpus luteum.


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