In VIVO UPTAKE AND METABOLISM OF [3H]PROGESTERONE AND [3H]5α-Dihydroprogesterone BY RAT CNS AND ANTERIOR PITUITARY: TISSUE CONCENTRATION OF PROGESTERONE ITSELF OR METABOLITES?

Karavolas, Harry J.; Hodges, Donald R.; O'Brien, D.

doi:10.1016/b978-0-08-023796-1.50122-5

Cited by 3 publications

(4 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding was also ob served in the immature PMSG-primed rat exposed to constant light after administration o f a single dose o f 5 « -D H P [5]. 5 « -D H P is present at proestrus in the ovarian vein blood [6,7] and it was showed to be specifically accumulated in the anterior pituitary 10 min after a single injection o f either [ ' H]-progesterone or [}H ]-5 a-D H P [8,11]. Formation o f 5 u -D H P by the hy pothalamus and pituitary in vitro has also been demonstrated [10].…”

Section: Discussionmentioning

confidence: 76%

“…Several studies have suggested that differential FSH and LH secretion can be explained by the modulation exerted by gonadal peptides [1][2][3]. However, in the estrogen-primed ovari ectomized rat and in the immature rat treated with preg nant mare serum gonadotropins (P M SG ), the progesterone metabolites 5a-dihydroprogesterone (5 «-D H P ; 5a-pregnane-3,20-dione) and 3a, 5a-tetrahydroprogesterone (3a, 5a-THP; 3a-hydroxy-5a-pregnane-20-one) have been shown to bring about selective release o f FSH and LH , respectively [4,5], These metabolites are secreted by the ovary during late proestrus [6,7] and [3H ]-5 a-D H P is rapidly taken up by the anterior pituitary when injected in the animal [8,9], Furthermore, rapid metabo lism o f progesterone to 5 a-D H P and 3a, 5a-TH P takes place in Received: October 11, 1989 Accepted after revision: December 20, 1989 the hypothalamus and pituitary [10,11], Based on the above observations, it has been suggested that progesterone may bring about selective secretion o f FSH and LH through its metabo lism [4,5,12,13].The mechanisms by which progesterone modulates the go nadotropin surge in estrogen-primed ovariectomized rats and cycling rats are multiple and are under extensive investigation. They include a rapid release of hypothalamic LH-releasing hor mone (LH R H ) [14,15], suppression o f enzymes that degrade L H R H [16] and a decrease in occupied nuclear estrogen recep tor (E2R) binding in the anterior pituitary [17,18].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibitory Effect of 5-Alpha-Dihydroprogesterone on Nuclear Estrogen Receptor Binding of the Anterior Pituitary and Uterus in the Rat

1990

View full text Add to dashboard Cite

Progesterone and its metabolite 5α-dihydroprogesterone (5α-DHP) have been shown to bring about gonadotropin release in the estrogen-primed ovariectomized rat. One of the actions of progesterone is the decrease in occupied estrogen receptors (E₂RS) in the anterior pituitary and uterus. This study attempted to determine if 5α-DHP had a similar effect on pituitary and uterine E₂RS. Estrogen-primed ovariectomized mature female rats were injected with either vehicle, or 0.2, 0.8 or 2 mg/kg body weight (BW) of 5α-DHP, 2 h before sacrifice and 1 h before the last estradiol injection (2 µg/rat). Nuclear E₂RS were determined by Scatchard analyses in the uterus and anterior pituitary. Total nuclear E2R levels of both tissues showed a 2-fold increase in the number of estradiol-binding sites after estradiol administration, as compared to control groups. In estradiol-primed rats, 5α-DHP produced a significant decrease in total nuclear E₂R levels in a tissue-specific manner. In the pituitary, there was a maximal and significant decrease in nuclear E₂RS with 0.2 and 2.0 mg/kg BW of 5α-DHP as compared to estradiol alone; the intermediate dose of 0.8 mg/kg BW of 5α-DHP induced a smaller nonsignificant change in nuclear E₂RS. In the uterus, 5α-DHP showed a dose-dependent decrease in nuclear E₂RS. The 5α-DHP effect in both tissues was due to a specific reduction in the occupied form of nuclear E₂RS levels. The unoccupied form of E₂RS was unaffected by 5α-DHP administration. 5α-DHP did not have any effect in the absence of estrogen priming. The acute tissue-specific decrease in occupied E₂RS induced by 5α-DHP was similar to that previously described by us with progesterone in the same animal model. The dose of 5α-DHP required was less than the dose of progesterone for comparable effects.

show abstract

Section: Discussionmentioning

confidence: 76%

mentioning

confidence: 99%

Inhibitory Effect of 5-Alpha-Dihydroprogesterone on Nuclear Estrogen Receptor Binding of the Anterior Pituitary and Uterus in the Rat

1990

View full text Add to dashboard Cite

show abstract

“…These may be due to the presence of small amounts of the progesterone receptor due to small amounts of estrogen from adrenal secretion and the peripheral aromatization of androgens. Furthermore, a population of estrogen-independent progesterone receptors has also been identified in the rat and hamster uterus [38,39]. Reduction of uterine ER binding in vitro by progesterone in the uteri of rats ovariectomized for 2 wk has also been reported [40].…”

Section: Discussionmentioning

confidence: 93%

Changes in Rat Uterine Estrogen Receptor Messenger Ribonucleic Acid Levels during Estrogen- and Progesterone-Induced Estrogen Receptor Depletion and Subsequent Replenishment1

Rosser

Chorich

Howard

et al. 1993

Biology of Reproduction

View full text Add to dashboard Cite

The overall objectives of this study were to determine whether the rapid decrease in estrogen receptor (ER) binding in the rat uterus after an injection of estradiol and subsequent recovery of ER levels was accompanied by similar changes in ER mRNA levels. Furthermore, the effect of progesterone administered under conditions known to decrease ER binding, in the rat uterus, on ER mRNA levels was also investigated. Ovariectomy for 14 days brought about a 3-fold increase in rat uterine ER mRNA levels, and these elevated levels were decreased by a 3-day treatment with 2 micrograms of estradiol in ethanol/saline injected i.p. In the ovariectomized rat, 1 and 5 micrograms of estradiol brought about small but significant decreases in ER mRNA levels in 1 h, which did not parallel the rapid decrease in ER binding at that time reported earlier. The 10-micrograms dose of estradiol brought about a bigger decrease in ER mRNA levels. In the ovariectomized rat primed with estradiol (2 micrograms/day in ethanol/saline), the administration of 2 micrograms of estradiol brought about no change in uterine ER mRNA levels at 6 h as compared to the 1-h time point if the values were not corrected for beta-actin, which was significantly increased at 6 h. A dramatic increase in ER mRNA levels 12 h after the estradiol injection preceded the increase in ER binding observed at 18 h. Progesterone (0.8 mg/kg body weight [BW]) in the absence of estrogen priming brought about minimal but significant inhibition of ER mRNA levels 12 and 18 h after administration, with no effects at 1 and 6 h. In the presence of estrogen priming, the 0.8-mg/kg BW dose of progesterone did not cause any changes in ER mRNA levels beyond those brought about by estrogen alone after 1 h, even though it has been shown to significantly decrease ER binding. This was also true when a larger dose of progesterone (2.0 mg/kg BW) was used, a dose that decreases ER binding to a significantly greater extent than the 0.8-mg/kg BW dose. However, the 4.0-mg/kg BW dose of progesterone decreased ER mRNA levels. Thus a single injection of estradiol appears to cause a decrease in ER binding primarily by accelerated receptor processing and degradation with small changes in ER mRNA within the first hour. A significant increase in uterine ER mRNA at 12 h precedes increased ER binding at 18 h. This indicates new synthesis of ER during the recovery period.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

“…The specific localization of progesterone by the target tissues has also been shown in a number of experiments (Laumas & Farooq, 1966;Davies & Ryan, 1972;Karavolas, Hodges & O'Brien, 1979;Moguilewsky & Raynaud, 1979;Roy, MacLusky & McEwen, 1979;Verma & Laumas, 1979;Walters & Clark, 1979;Stone & Miller, 1980). However, knowledge of the mode of action of progesterone in general is still far from complete but studies on blood levels, tissue distribution and the metabolic fate of progesterone under physiological conditions should help in this understanding.…”

Section: Introductionmentioning

confidence: 81%

Fate of Progesterone in the Plasma and Various Tissues of Anaesthetized Rabbits

Verma¹,

Laumas²

1981

Journal of Endocrinology

View full text Add to dashboard Cite

Studies on the metabolism of progesterone in rabbit plasma and tissues during constant infusion of [3H]progesterone revealed a gradual increase in the concentration of progesterone in plasma until a state of equilibrium was attained about 2 h after the start of infusion. The metabolic clearance rate of progesterone was 0.116 l/min and the turn-over time was 0.006 min/ml plasma. Under conditions of equilibrium, the concentration of radioactivity as well as that of labelled progesterone was higher in the tissues than in plasma. On a unit-weight basis, myometrium localized 6.6 nCi, Fallopian tube 5.5 nCi and vagina 6.1 nCi [3H]progesterone/g tissue. A higher concentration of progesterone, 16.5 nCi, was localized in the mammary gland tissue. Skin localized only 0.9 nCi progesterone and the lowest amount (0.34 nCi/ml) was found in plasma. The metabolism of progesterone in tissues differed from that in plasma. In plasma only 5.6% of the infused steroid was recovered as unconverted progesterone and the major amount was metabolized to polar compounds with smaller amounts of 5 alpha-pregnane-3,20-dione, 5 alpha-pregnan-3 beta-ol-20-one and 20 alpha hydroxypregn-4-en-3-one. In the myometrium and Fallopian tubes the major metabolites were 5 alpha-pregnan-3 beta-ol-20-one and 5 alpha-pregnane-3,20-dione respectively. In the vagina, like the myometrium, 5 alpha-pregnan-3 beta-ol,20-one was the major metabolite. 20 alpha-Hydroxypregn-4-en-3-one was the major identified metabolite of mammary gland tissue.

show abstract

In VIVO UPTAKE AND METABOLISM OF [3H]PROGESTERONE AND [3H]5α-Dihydroprogesterone BY RAT CNS AND ANTERIOR PITUITARY: TISSUE CONCENTRATION OF PROGESTERONE ITSELF OR METABOLITES?

Cited by 3 publications

References 41 publications

Inhibitory Effect of 5-Alpha-Dihydroprogesterone on Nuclear Estrogen Receptor Binding of the Anterior Pituitary and Uterus in the Rat

Inhibitory Effect of 5-Alpha-Dihydroprogesterone on Nuclear Estrogen Receptor Binding of the Anterior Pituitary and Uterus in the Rat

Changes in Rat Uterine Estrogen Receptor Messenger Ribonucleic Acid Levels during Estrogen- and Progesterone-Induced Estrogen Receptor Depletion and Subsequent Replenishment1

Fate of Progesterone in the Plasma and Various Tissues of Anaesthetized Rabbits

Contact Info

Product

Resources

About