REDUCTIVE PATHWAYS OF PROGESTERONE METABOLISM IN THE RAT OVARY

1972 ◽  
Vol 69 (1) ◽  
pp. 141-152 ◽  
Author(s):  
A. Zmigrod ◽  
H. R. Lindner ◽  
S. A. Lamprecht

ABSTRACT Progesterone underwent extensive reductive metabolism when incubated with a microsomal preparation from rat ovaries in the presence of NADPH. The major products formed were 3β-hydroxy-5α-pregnan-20-one, 5α-pregnane-3,20-dione and 5α-pregnane-3β,20α-diol. Newly formed corpora lutea of pregnancy were almost devoid of any microsomal A-ring reducing activity (5α-reductase and a 3β-hydroxysteroid dehydrogenase) and of soluble 20α-hydroxysteroid dehydrogenase. The behaviour of the A-ring reducing enzymes paralleled that of 20α-ol dehydrogenase in that their activity (i) was high during the oestrous cycle; (ii) declined between the third and seventh day of pregnancy; and (iii) increased sharply in corpora lutea of pregnancy when ergocornine – a drug blocking pituitary prolactin secretion – was given to the rats, yet remained low when prolactin and ergocornine were administered concurrently. However, the A-ring reducing activity did not show the sharp pre-partum rise exhibited by 20α-ol dehydrogenase, thus deviating from a pattern compatible with a co-ordinate control of the three enzymes involved in the metabolic inactivation of progesterone. Contrary to a report in the literature, 5α-pregnane-3,20-dione (20 mg/rat/day) was found to be ineffective when tested for pregnancy or deciduoma supporting activity in ovariectomized rats. The microsomal reductases, if indeed operative in vivo, may restrict the availability of progesterone as an oestrogen precursor.


1964 ◽  
Vol 12 (9) ◽  
pp. 670-673 ◽  
Author(s):  
KÁROLY BALOGH

20α-Hydroxysteroid dehydrogenase activity was localized histochemically in the corpus luteum of the rat by using Nitro-BT as an indicator. Intensive enzyme activity was obseryed in the corpus luteum cells, especially during involution. The placenta and corpora lutea of pregnancy failed to reveal enzyme activity during the last week of gravidity. Other tissues, including endocrine glands, liver and kidneys were also negative. The Present method offers a possibility to identify the sites of progesterone metabolism in the rat ovary at the microscopic level.



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.



Endocrinology ◽  
1994 ◽  
Vol 135 (4) ◽  
pp. 1477-1487 ◽  
Author(s):  
S Ghersevich ◽  
P Nokelainen ◽  
M Poutanen ◽  
M Orava ◽  
H Autio-Harmainen ◽  
...  


1972 ◽  
Vol 69 (1) ◽  
pp. 127-140 ◽  
Author(s):  
A. Zmigrod ◽  
H. R. Lindner

ABSTRACT Ovarian homogenates or microsomes from pregnant rats were capable of aromatizing C19-steroids (testosterone or androstenedione) in the presence of NADPH to form oestrone and 17β-oestradiol; the microsomal preparation was also capable of forming these oestrogens from progesterone. The rate of oestrogen formation from either type of substrate increased during the first week of pregnancy. Aromatizing activity reached a plateau by about the fifth to sixth day after mating, at a level similar to that found in the ovaries of pro-oestrous rats. Side-chain cleaving activity continued to rise until the seventh day of pregnancy, yet remained far below that in pro-oestrous animals. Hence side-chain cleavage, rather than aromatizing activity, must limit oestrogen formation during early pregnancy. Isolated corpora lutea of pregnancy and the remainder of the ovary, consisting of involuting corpora lutea, small follicles and interstitial tissue, contributed about equally to ovarian oestrogen production from progesterone under the in vitro conditions. Neither aromatizing nor side-chain splitting activity showed a distinct peak on the fourth day of pregnancy, the time of the putative prenidatory oestrogen surge.



1987 ◽  
Vol 25 (3) ◽  
pp. 160-170 ◽  
Author(s):  
F. López ◽  
D. González ◽  
E. Aguilar


1998 ◽  
pp. 594-600 ◽  
Author(s):  
T Shimamoto ◽  
M Yamoto ◽  
R Nakano

OBJECTIVES: Our purpose was to elucidate the involvement of the tyrosine kinase pathway in gonadotropin-induced ovulation in the rat ovary. STUDY DESIGN: We investigated the effect of a tyrosine kinase inhibitor, tyrphostin, on the rat ovulatory process in vivo and in vitro. METHODS: In cultured rat granulosa cells, the effect of tyrphostin on LH-, dibutyryl cyclic AMP ((Bu)2cAMP)- or forskolin-stimulated tissue type plasminogen activator (tPA) activities was examined by using a fibrin autography technique. In an in vivo system, tyrphostin was injected into the bursal cavity of the ovary in pregnant mare serum gonadotropin-treated rats, just before human chorionic gonadotropin administration. After 24 h, the number of oocytes in the oviduct was counted and the tyrphostin-treated ovaries were examined histologically. RESULTS: Tyrphostin inhibited LH-stimulated tPA activity but did not affect (Bu)2cAMP- or forskolin-stimulated ones. In an in vivo study, tyrphostin suppressed oocyte release dose-dependently. Histological observations revealed that tyrphostin-treated ovaries contained many large unruptured follicles and a few corpora lutea. CONCLUSION: This study suggests that the suppressive effect of tyrphostin on ovulation may be partly due to tPA activity inhibition in the granulosa cells via the suppression of tyrosine kinase activity. Additionally, tyrosine kinase phosphorylation may be involved in gonadotropin-activated signaling systems in the rat ovulatory process.



1990 ◽  
Vol 124 (3) ◽  
pp. 425-432 ◽  
Author(s):  
P. van der Schoot ◽  
J. Th. J. Uilenbroek ◽  
E. J. Slappendel

ABSTRACT Treatment of female rats for 3 weeks with the antigestagen 1 1β-(4-dimethylaminophenyl)-17β-hydroxy-17α-(prop-1 -ynyl)-estra-4,9-dien-3-one (mifepristone) results in pituitary and ovarian enlargement. The present study dealt with the possible mechanism(s) of these responses. Ovarian enlargement appeared to be dependent upon prolactin. In the absence of prolactin, during combined treatment with mifepristone and the dopamine agonist 2-Br-α-ergokryptine, ovarian growth was significantly suppressed. It was unclear why persistent hyperprolactinaemia, due to treatment with mifepristone, resulted in persistence of functionally active corpora lutea despite intermittent ovulation, while persistent hyperprolactinaemia due to ectopic pituitary grafts did not. Pituitary enlargement appeared to be dependent upon the persistence of ovarian oestrogen secretion during the treatment period. Ovariectomy or lactation fully inhibited this response. Pituitary enlargement and prolactin secretion in ovariectomized rats in response to exogenous oestrogen (injections of oestradiol benzoate) were significantly enhanced by additional treatment with mifepristone. It is concluded that mifepristone facilitates the effect of oestrogen on pituitary lactotrophs, thereby enhancing pituitary growth. Ovarian enlargement during treatment with mifepristone may be specific for rats due to the luteotrophic action of prolactin in these animals. Pituitary enlargement due to facilitation of oestrogen-induced pituitary growth may become a focus of attention when this or similar antigestagenic drugs are being used for prolonged periods in clinical trials, e.g. for limiting steroid-sensitive tumour growth. Journal of Endocrinology (1990) 124, 425–432



1984 ◽  
Vol 247 (4) ◽  
pp. E483-E488
Author(s):  
M. Haji ◽  
G. S. Roth ◽  
M. R. Blackman

Various in vivo and in vitro pituitary lactotropic and gonadotropic functions were measured in mature (6-7 mo, normally cycling) and old (24 mo, constant diestrus) female Wistar rats. Serum prolactin (PRL) levels were higher (P less than 0.001), whereas luteinizing hormone (LH) values were similar (P greater than 0.05) in old versus mature rats both before and 3 days after ovariectomy. Serum PRL levels decreased significantly (P less than 0.005) postovariectomy only in the mature rats. The in vitro release of PRL and LH was measured for 4 days in primary adenohypophyseal cell cultures from the ovariectomized rats. Both basal and 17 beta-estradiol (E2)-stimulated PRL release (P less than 0.001) and production (P less than 0.005) were greater by cells from old rats. In contrast, both basal release and E2-stimulated LH release were greater (P less than 0.001) by cells from mature rats. Peak PRL release by cells from both old and mature rats occurred after exposure to E2 doses 1/100th of those required for peak LH release. These data support the hypothesis that intrinsic derangements in anterior pituitary function contribute to the reproductive decline in aging female rats and that different pituitary cell types exhibit discordant age changes in estrogenic sensitivity.



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