STUDIES ON THE PATTERN OF CIRCULATING STEROIDS IN THE NORMAL MENSTRUAL CYCLE

1977 ◽  
Vol 84 (3) ◽  
pp. 620-632 ◽  
Author(s):  
B.-M. Landgren ◽  
A.-R. Aedo ◽  
M. Nuñez ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT By the use of a non-thrombogenic pump, blood was withdrawn continuously at a rate of 4.0 ml/h over a period of 48 h from 10 normally menstruating women during various phases of the peri-ovulatory period and the integrated levels of oestradiol, oestrone, 17-hydroxyprogesterone, progesterone, 20α-dihydroprogesterone and biologically active luteinizing hormone (LH) were estimated in 3-hourly plasma collections. The first significant change detected two days prior to the LH surge (day LH-2) in one subject studied during this period was a continuous parallel rise in oestradiol and oestrone levels, which occurred in the absence of any simultaneous change in LH and 17-hydroxyprogesterone levels. Marked fluctuations followed by a sudden drop in oestradiol levels were observed in another woman during the day preceding the LH peak (day LH-1). These changes were not associated with similar alterations in oestrone levels. The marked drop in oestradiol coincided with the beginning of a simultaneous major rise in LH and 17-hydroxyprogesterone levels followed some 6 to 9 h later by a small but significant increase in progesterone levels. The period of the LH surge (day LH) was studied in 3 women. This period was characterised by a constant decline in oestradiol levels in the presence of unchanged oestrone values. The decrease in oestradiol levels preceded the LH peak by at least 12 h. The LH peak was biphasic in all subjects; both the ascending and descending limbs of it were significantly correlated to similarly changing levels of 17-hydroxyprogesterone. The increase in these two hormones preceded that in progesterone levels, which occurred later, at the time of the steepest rise in LH levels. The findings of the subsequent day (day LH+1) were characterised in two subjects by a parallel decrease in plasma oestradiol, LH and 17-hydroxyprogesterone levels, until a plateau was reached. This plateau coincided with a new rise in progesterone and 20α-dihydroprogesterone levels. The hormonal profile observed two days following the LH surge (day LH + 2) in 3 women was similar to that of the preceding day, with the exception of a beginning new rise in 17-hydroxyprogesterone levels by the end of day LH + 2. This second rise in 17-hydroxyprogesterone paralleled that in progesterone and 20α-dihydroprogesterone levels and occurred in the presence of decreasing levels of LH. The data reported strongly suggest that different control mechanisms are involved in the regulation of ovarian steroid secretion during the various phases of the peri-ovulatory period.

1976 ◽  
Vol 82 (3) ◽  
pp. 600-616 ◽  
Author(s):  
A.-R. Aedo ◽  
B.-M. Landgren ◽  
Z. Cekan ◽  
E. Diczfalusy

ABSTRACT Plasma levels of 20α-dihydroprogesterone, 17-hydroxyprogesterone and 17-hydroxypregnenolone were assayed daily in 15 normally menstruating women during a complete menstrual cycle. In order to ascertain the normalcy of the cycles studied, LH, progesterone and oestradiol were also determined daily. The pattern of 20α-dihydroprogesterone was very similar to that of progesterone. The levels found during the proliferative phase (around 240 pg/ml) increased significantly on the day of the LH-surge and reached values of approximately 3.7 ng/ml at the peak period of luteal activity. The plasma levels of 17-hydroxyprogesterone in the proliferative phase were around 380 pg/ml. The first significant increase occurred one day before the LH-surge and was followed by a sharp peak (approximately 1.5 ng/ml) which coincided with the LH peak. A significant decrease occurred after this first peak, which reached a nadir two days after the LH-surge. This was followed by a second rise with a rather broad peak (about 1.8 ng/ml) around the 5th to 7th days after the LH-surge. The levels of 17-hydroxypregnenolone did not show any cyclic variation: from all figures a geometric mean value of 1.62 ng/ml was calculated with tolerance limits at 0.241 and 10.8 ng/ml. Individual day-to-day changes in steroid levels were assessed with regard to their potential for the early identification of the day of the LH-surge. A 17-hydroxyprogesterone value of 1.0 ng/ml, or more, was seen for the first time in the cycle on the day of the LH peak in 13 cycles and a progesterone + 17-hydroxyprogesterone level of at least 1.8 ng/ml in 14 of the 15 cycles studied. These data seem to warrant a study of the predictive value of progesterone and 17-hydroxyprogesterone assays in a much larger population.


1977 ◽  
Vol 86 (3) ◽  
pp. 608-620 ◽  
Author(s):  
B.-M. Landgren ◽  
S. Campo ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT The variation of the plasma levels of 11 steroids and LH was investigated in 6 normally menstruating women during the peri-menstrual period. Blood was withdrawn continuously over a period of 42 h at a rate of 4 ml/h by means of a non-thrombogenic pump. The changes in hormone levels were studied during 14 3-h sampling periods (42 h) which - with respect to the clock time - were identical in all subjects. Cortisol, 17-hydroxypregnenolone and dehydroepiandrosterone exhibited a marked circadian rhythm with the highest mean levels in the morning between 06.00 and 09.00 h and the lowest mean levels during the night between 21.00 and 03.00 h. The amplitude of the variation was high, the differences between the highest and lowest values being 200, 590 and 150%, respectively. Also the coincidence of individual peak values with the average peaks was high (mostly in 5 out of 6 cases). The correlation of cortisol levels with those of 17-hydroxypregnenolone and dehydroepiandrosterone was significant (r = 0.79 and 0.59, respectively; P < 0.001). The circadian variation of 17-hydroxyprogesterone, androstenedione and pregnenolone was also significant, but less pronounced, as indicated by lower amplitudes and larger spread of individual peaks around average peaks. The correlation of the levels of these steroids with those of cortisol was significant (r=0.47 P<0.001; r=0.44 P<0.001 and r=0.31: P<0.01, respectively). Progesterone, 20α-dihydroprogesterone, testosterone and oestradiol did not exhibit any circadian variation, but a steady decrease of levels. The levels of the first two steroids were significantly correlated (r = 0.81; P < 0.001). The dihydrotestosterone and LH levels did not show any significant changes during the entire study. If, however, only the second half of the sampling time was statistically analysed, a significant increase was found in the LH levels. During this time the LH levels were negatively correlated with the decreasing levels of progesterone and 20α-dihydroprogesterone (r=−0.59 and −0.66, respectively; P < 0.001). A comparison of the data with those of a previous study performed during the peri-ovulatory period suggests that the occurrence, intensity and regularity of the circadian rhythm varies according to different phases of the menstrual cycle. The data also suggest that 17-hydroxypregnenolone in plasma is an excellent indicator of adrenocortical activity.


1980 ◽  
Vol 93 (3) ◽  
pp. 257-263 ◽  
Author(s):  
A. Miyake ◽  
Y. Kawamura ◽  
T. Aono ◽  
K. Kurachi

Abstract. The plasma concentrations of immunoreactive LRH, LH, FSH, oestradiol and progesterone were measured daily by a sensitive double antibody radioimmunoassay during 12 cycles of 8 normal cyclic women. The mean (± se) immunoreactive LRH levels in the follicular and luteal phase except the immunoreactive LRH peaks during normal cycles were 4.18 ± 0.38 pg/ml and 4.50 ± 0.45 pg/ml, respectively. The immunoreactive LRH peaks were observed in 11 of 12 cycles, appearing on day −4 to −1 from the LH surge in 9 cycles and on day +1 and +2 in 2 cycles. The mean value of immunoreactice LRH peaks was 42.0 ± 11.4 pg/ml with range of 12 to 154 pg/ml. The immunoreactive LRH peak lasted for one day in 10 cycles and for 4 days in one cycle. The immunoreactive LRH peaks in different cycles of the same women did not occur on the same day relative to the LH peak. The plasma immunoreactive LRH levels measured every 10 min for 40 min periods every day in normal cyclic women during the ovulatory phase showed slight, but not significant fluctuations. Plasma oestradiol levels began to increase on day −6, reaching a peak on day − 1, and were followed by peaks of LH and FSH. These data indicate that increase in serum oestradiol was followed by release of LRH from the hypothalamus and pre-ovulatory discharge of gonadotrophins from the pituitary.


1977 ◽  
Vol 86 (3) ◽  
pp. 621-633 ◽  
Author(s):  
M. Nuñez ◽  
A.-R. Aedo ◽  
B.-M. Landgren ◽  
S. Z. Cekan ◽  
E. Diczfalusy

ABSTRACT The plasma levels of oestrone sulphate, oestradiol sulphate, oestrone and oestradiol were studied in samples collected daily from 8 normally menstruating women throughout a complete menstrual cycle. In order to ascertain the normality of the cycles studied, LH and progesterone were also determined daily. All compounds were measured by radioimmunoassay, the sulphates after solvolysis. For the determination of the sulphates a procedure was developed which fulfilled the recognized criteria of reliability. Both oestrone sulphate and oestradiol sulphate displayed a marked cyclic pattern, similar to and correlated with that of oestrone and oestradiol, i. e., all 4 oestrogens exhibited a marked mid-cycle peak and elevated levels during the luteal phase. The mean levels of the steroid moiety of oestrone sulphate were 10–15 times higher than those of oestrone, and 2–3 times higher than those of the 3 other oestrogens together. On the other hand, the mean levels of oestradiol sulphate were 1.2 to 4 times lower than those of oestradiol. The ratios of the levels of various pairs of oestrogens were calculated. All pairs showed a considerable change of ratios from the early follicular phase to mid-cycle. This demonstrates that the mutual metabolic equilibria of oestrogens are different in various phases of the cycle. Daily measurements of oestrone sulphate and oestradiol sulphate do not seem to provide a better index to predict the day of ovulation than the characteristic changes in progesterone and 17-hydroxyprogesterone levels.


1974 ◽  
Vol 76 (3) ◽  
pp. 556-569 ◽  
Author(s):  
E. Nieschlag ◽  
K. H. Usadel ◽  
H. K. Kley ◽  
U. Schwedes ◽  
K. Schöffling ◽  
...  

ABSTRACT A new method for the investigation of hypothalamo-pituitary-gonadal and adrenal feedback control mechanisms based on the biological neutralization of gonadal and adrenal steroids by active immunization is proposed. The regulatory influence of a given steroid in the feedback control is proved when reduction of the free, biologically active fraction of this steroid caused by antibody binding induces a positive response of the pituitary, thus effecting gonadal or adrenal hypertrophy and hyperfunction. The advantages and limitations of the new model are demonstrated by the effects of active immunization of rabbits with cortisol (F), aldosterone (Aldo), dehydroepiandrosterone (DHA), androstenedione (Δ4-A), testosterone (T), 5α-dihydrotestosterone (5α-DHT), 5β-DHT and oestradiol (E2). In the immunized animals and in a control group serum concentrations of total corticosteroids (TC), DHA, T, Δ4-A, E1, E2, LH and FSH, the percentage of binding of steroids in serum and the specificity of the antisera are determined. The testes are evaluated by histometry and the nuclear volume of the adrenocortical and Leydig cells is measured.


1990 ◽  
Vol 259 (4) ◽  
pp. L185-L197
Author(s):  
B. R. Stripp ◽  
J. A. Whitsett ◽  
D. L. Lattier

Gene transcription is regulated by the formation of protein-DNA complexes that influence the rate of specific initiation of transcription by RNA polymerase. Recent experimental advances allowing the identification of cis regulatory sequences that specify the binding of trans acting protein factors have made significant contributions to our understanding of the mechanistic complexities of transcriptional regulation. These methodologies have prompted the use of similar strategies to elucidate transcriptional control mechanisms involved in the tissue specific and developmental regulation of pulmonary surfactant protein gene expression. The purpose of this review is to describe various methodologies by which molecular biologists identify and subsequently assay regions of nucleic acids presumed to be integral in gene regulation at the level of transcription. It is well established that genes encoding surfactant proteins are subject to regulation by hormones, cytokines, and a variety of biologically active reagents. Perhaps future studies utilizing molecular tools outlined in this review will be valuable in identification of DNA sequences and protein factors required for the regulation of lung surfactant genes.


1988 ◽  
Vol 117 (3) ◽  
pp. 447-453 ◽  
Author(s):  
S. A. Nicholson ◽  
M. Aslam ◽  
T. T. Chuang ◽  
B. Gillham ◽  
M. T. Jones

ABSTRACT Female Wistar-derived rats with regular oestrous cycles were injected s.c. at 15.00 h on pro-oestrus with difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase. The drug (10–100 mg/rat) caused a dose-related reduction in the concentration of LH in plasma taken at 19.00 h (the time of the peak of the LH surge in this colony). There was also a dose-related reduction in the pituitary content of total polyamines. The reduction in the plasma concentration of LH was not due to the shifting of the time of the peak of the surge, as concentrations were significantly lower than control from 17.00 to 21.00 h, the overall reduction in total LH release being approximately 50%. The number of ova in the oviducts at 06.00 h next morning was significantly reduced by treatment with 50 mg DFMO/rat, by an average of 70%. Injection of DFMO enhanced the fall in plasma oestradiol concentrations seen between 15.00 and 19.00 h, in a dose-related manner. It also prevented the rise in progesterone concentrations seen in control animals during this period. The ability of DFMO to prevent the rise in plasma concentrations of LH was not secondary to the effects of the drug on ovarian steroid production because DFMO also significantly reduced the LH surge in animals ovariectomized on dioestrus and given appropriate replacement injections of oestradiol and progesterone. It seems possible that part of the action of DFMO is exercised at the hypothalamus, since when 50 mg DFMO/rat was given either 2 or 4 h before the expected peak of the LH surge, the LHRH content of the hypothalamus was significantly reduced at that time. These results suggest that activation of ornithine decarboxylase is a necessary prerequisite for a normal LH surge, and that this activation is steroid-dependent. This conclusion is borne out by results from direct observations on the activity of the enzyme in pituitary tissue incubated in vitro. J. Endocr. (1988) 117, 447–453


1983 ◽  
Vol 104 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Caroline Smith ◽  
A. M. Perks

Abstract. The pre-ovulatory fall in plasma kininogens in rats with 4 day oestrous cycles started between 12.00 and 15.00 h pro-oestrus, reached a maximum decline of 51% by 18.00 h pro-oestrus, and started to recover before ovulation. Because these changes appeared to correspond with the LH-surge, and to follow the peak in plasma oestradiol-17β levels, both of these hormones were tested for possible effects on plasma kininogens. Intracardiac injections of 110 IU of equine LH into dioestrous rats were followed by a decline of 30.8 ± 6.7% in plasma kininogens, 6 h after injection (significant, P< 0.01). Values were still depressed, but recovering, 12 h after treatment; the reduction was 21.3 ± 5.8% (significant, P < 0.01). Controls showed no decline. Injections of oestradiol-17β (1.0 μg/100 g body weight) produced no significant effects. It is suggested that the LH surge may be responsible, at least in part, for the decline in plasma kininogens seen before ovulation.


1975 ◽  
Vol 79 (2) ◽  
pp. 329-336 ◽  
Author(s):  
F. Lehmann ◽  
I. Just-Nastansky ◽  
B. Behrendt ◽  
P.-J. Czygan ◽  
G. Bettendorf

ABSTRACT The effect of orally given diethylstilboestroldiphosphate (DES) and 17α-ethinyl-oestradiol-3-methylether (EEM) on plasma progesterone levels was studied. Both compounds were administered for 5 days to 5 women in daily doses of 60 mg (DES) and 30 mg (EEM). The fully informed volunteers were found to have a normal menstrual cycle before the study. The mean corpus luteum phase (corpus luteum phase = days between LH surge and onset of menstruation) of all control cycles lasted 12.8 days. Daily plasma samples were collected for radioimmunoassay (RIA) of progesterone, immunoreactive oestrogens and LH. After a control cycle the first treatment was carried out with DES. The third and the fifth cycle were control cycles again. The EEM-treatment was done in the fourth cycle. Although the effect of the two compounds was different, a dependence of the age of the corpus luteum (CL) could be demonstrated for both. DES-treatment lowered plasma progesterone levels during administration. This effect was only demonstrable if the treatment was begun on the day of the LH-peak. The length of the CL-phase remained unaltered. EEM-treatment if started on the day of the LH surge, suppressed corpus luteum function in the late luteal phase. If the treatment was started later, the effect was less pronounced. The administration of both compounds did not shorten the time between ovulation and the next bleeding. After DES-treatment this interval was not altered. After EEM-treatment the subsequent bleeding was even delayed depending on slowly decreasing levels of plasma oestrogens.


1985 ◽  
Vol 68 (6) ◽  
pp. 639-645 ◽  
Author(s):  
K. Lafferty ◽  
J. C. De Trafford ◽  
C. Potter ◽  
V. C. Roberts ◽  
L. T. Cotton

1. Raynaud's phenomenon is a condition which primarily affects women and it must be assumed that hormonal influences are responsible. 2. To further investigate this assumption the effect of cyclic sex hormone fluctuations on the digital vascular reactivity of ten normal young women was studied by the diagnostic techniques of thermal entrainment of finger blood flow and Doppler ultrasound mapping of the digital arteries. 3. In the immediate pre-ovulatory period the results obtained were comparable with those found in patients with established Raynaud's phenomenon, suggesting that oestrogen has an important modulating effect in vivo on reflex peripheral vasomotor responses to thermal stimuli. 4. ‘Primary’ Raynaud's phenomenon may represent an exaggerated response to oestrogen.


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