Pituitary responsiveness to LH-RH and TRH and the effects of progesterone or progesterone and oestradiol treatment in anoestrous sheep.

Pituitary responsiveness to 200 microgram synthetic LH-RH and to 10 microgram TRH was determined in anoestrous sheep before and after treatment for 3 weeks with progesterone (100 mg/day), or oestradiol (250 microgram/day) plus progesterone (100 mg/day). There was a marked decrease in pituitary responsiveness to LH-RH after progesterone (P is less than 0.01), or oestradiol plus progesterone (P is less than 0.01) treatments, and an increase in response to TRH after oestradiol plus progesterone (P is less than 0.01) treatment. The results demonstrate selective and simultaneous feedback effects of oestradiol and progesterone on pituitary responsiveness to two hypothalamic releasing hormones.     

Copulatory behavior of sexually inexperienced male hamsters paired with natural proestrous females

The copulatory behavior of sexually inexperienced male hamsters paired with natural proestrous females was observed between 1900 and 2000 hours under dim red light illumination. Each male was allowed 30 min to mate with a receptive female. Five out of 7 males showed at least one ejaculation within 30 min. Although the copulatory behavior of the above males was observed again, the activities of copulatory behavior did not facilitate.     

Self-priming effect of LH-RH on pituitary gonadotropins in hyperprolactinemic women

To investigate how various concentrations of serum prolactin (PRL) influence the priming effect of luteinizing hormone releasing hormone (LH-RH) on the pituitary gland, 24 women with various blood PRL concentrations received intravenous injections of 100 micrograms of synthetic LH-RH twice at an interval of 60 minutes and their serum LH and follicle-stimulating hormone (FSH) were measured and analysed. In the follicular phase with a normal PRL concentration (PRL less than 20 ng/ml, n = 6), marked first peaks of the two hormones following the first LH-RH stimulation and enhanced second peaks after the second LH-RH administration were observed, indicating a typical priming effect of LH-RH on gonadotropins, though the second response of FSH was more moderate than that of LH. In hyperprolactinemia, in which the serum PRL concentration was higher than 70 ng/ml (n = 13), the basal concentration of gonadotropins was not significantly changed but the priming effect of LH-RH on LH and FSH was significantly decreased (p less than 0.01). No marked second peaks of LH and FSH were observed, suggesting an inhibitory effect of hyperprolactinemia on the second release of LH and FSH. In contrast, this effect was restored in a group of women whose serum PRL concentration was between 30 and 50 ng/ml (n = 5). Furthermore, enhanced second peaks of both LH and FSH were noted after successful bromocriptine therapy reduced hyperprolactinemia (PRL greater than 70 ng/ml) to less than 25 ng/ml (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)     

Light-dark entrainment of proestrous LH surges and circadian locomotor activity in female hamsters

The temporal relationships of the proestrous LH surge and the circadian locomotor activity rhythm were compared in hamsters entrained to four different 24-hr light-dark (LD) cycles. Animals were housed in cages equipped with running wheels to obtain continuous activity records. Stable entrainment of locomotor activity was complete within 3 weeks of exposure to each photoperiod at which time hamsters were randomly assigned to hourly sample groups. Serum was obtained by cardiac puncture under light ether anesthesia on the day of proestrous and was assayed by RIA for LH. A computer-based least-squares sine wave-fitting technique determined a single objective phase reference point for the time of the hormone maximum. In each photoperiod, precise temporal relationships were maintained between the LH surge and activity onset, whereas the phase relationship between the LH surge and the LD cycle was more variable. These data indicate that the environmental LD cycle entrains the circadian timing system which, in turn, provides temporal information to the rhythms of proestrous gonadotropin and locomotor activity.     

Mechanism of the postcoital contraceptive effect of LH-RH in the rat. I. Serum hormone levels during chronic LH-RH Administration.

The mechanism of the postcoital contraceptive effect of luteinizing hormone-releasing hormone (LH-RH) was studied in the rat. 200 mcg of LH-RH administered daily over Days 1-7 of pregnancy produced a dramatic inhibition of pregnancy. This inhibition was directly correlated with induced 'surges' in serum LH over Days 1-4. Serum follicle stimulating hormone and prolactin were, in general, reduced over this same time period. A 48-hour delay in the preimplantation (Day 3) 'surge' in serum estradiol accompanied by a significant (ps less than .05 and less than .01) reduction in serum progesterone on Days 3, 4, 6, and 7 was also observed. The delayed 'surge' in serum estradiol on Day 5 and reduction in serum progesterone was correlated with an increase in folliculogenesis and luteolysis of established corpora lutea, respectively. These data suggest that in the rat LH-RH induces a rise in serum LH which is luteolytic during pregnancy and delays the serum estradiol surge necessary for normal implantation.     

Meiosis-inhibiting effects in vivo of antiserum to progesterone on follicular ova in immature rats treated with gonadotropins

Effects of the neutralization of endogenous progesterone with rabbit antiserum to progesterone (anti-progesterone) on germinal vesicle breakdown of ova in follicles of small (less than 125 micrometers), intermediate (125-250 micrometers) and large (greater than 250 micrometers) diameter were examined by a quantitative histological technique. Immature rats were treated with 5 IU pregnant mare's serum gonadotropin (PMS) then with 10 IU human chorionic gonadotropin (hCG). Administration of anti-progesterone together with hCG 6 h later significantly decreased the incidence of germinal vesicle breakdown of ova in the large follicles, but not in the intermediate ones. This treatment did not affect the proportion of intermediate to large follicles in the population. Replacement with progesterone 1 h after the simultaneous injection of hCG and anti-progesterone partly reversed the reduced incidence of meiosis. An injection of rabbit antiserum to estrone, in addition to the replacement with progesterone 1 h after the simultaneous injections of hCG and anti-progesterone, restored the incidence of meiosis to a value comparable to the values found for control rats treated sequentially with PMS and hCG. We concluded that the hCG-induced preovulatory rise in progesterone has a limited but definite stimulatory effect on the resumption of meiosis in the ova of large follicles and that it mediates the meiosis-inducing action of hCG.     

Serum prolactin levels in fetal and neonatal hamsters and the relationship to maternal levels.

Immunoreactive prolactin was measured by RIA in 13.5-15.5 day gestation fetal and 0.5-3.5 day neonatal hamster serum and found to significantly reflect rises and falls in maternal levels. On the average, fetal and neonatal levels were 37% of maternal prolactin serum levels. 125I-PRL injected into 13.5-15.5 day pregnant hamsters was demonstrated to cross the placenta and enter fetal circulation. Ten min after injection, fetal serum levels were calculated to be an average of 3.9% of the radioactivity recorded in maternal serum. There is a strong possibility that fetal prolactin serum levels may be, at least in part, attributed to a maternal source.     

Serum hormone levels during a post-implantation LH-RH induced luteolysis in the rat.

Daily administration of LH-RH (100 micrograms sc at 0900 and 1500 h) to rats over day 7-12 (D7-12) of pregnancy induced reovulation by D9 and a sustained decrease in uterine:fetal weight and vaginal bleeding by 0600 h on D10 of pregnancy. Serum hormone levels determined at 0600, 1200, and 2000 h over D7-12 of pregnancy revealed that luteinizing hormone (LH) was significantly elevated after each administration of LH-RH, while prolactin (PRL) was not significantly altered in any systematic fashion. An acute decline in serum progesterone at 2000 h on D7-9 following LH-RH administration was not sustained until after 0600 h on D10 when serum 20 alpha-dihydroprogesterone (20 alpha-hydroxy-4-pregnen-3-one, 20 alpha-DHP) in LH-RH treated animals rose significantly above control (2000 h, D10) and remained elevated throughout D11-12. Progesterone and 20 alpha-DHP values were reflected morphologically after D10 as the corpora lutea of LH-RH treated rats underwent luteolysis. A peak in serum estradiol levels in control animals was observed at 0600 h on D9. Serum estradiol-17 beta levels in LH-RH treated animals were similar to control except at 2000 h on D8 and D12 when LH-RH induced a significant increase. These observations suggest that subsequent to implantation in the rat, the temporal sequence of a decrease in progesterone secretion, luteolysis and pregnancy failure in response to LH-RH does not result from an increase in estradiol secretion attendant to reovulation.     

Extension of oestrous cycles and prolonged secretion of progesterone in non-pregnant cattle infused continuously with oxytocin

The experimental objective was to evaluate how continuous infusion of oxytocin during the anticipated period of luteolysis in cattle would influence secretion of progesterone, oestradiol and 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM). In Exp. I, 6 non-lactating Holstein cows were infused with saline or oxytocin (20 IU/h, i.v.) from Day 13 to Day 20 of an oestrous cycle in a cross-over experimental design (Day 0 = oestrus). During saline cycles, concentrations of progesterone decreased from 11.0 +/- 2.0 ng/ml on Day 14 to 2.0 +/- 1.3 ng/ml on Day 23; however, during oxytocin cycles, luteolysis was delayed and progesterone secretion remained near 11 ng/ml until after Day 22 (P less than 0.05). Interoestrous interval was 1.6 days longer in oxytocin than in saline cycles (P = 0.07). Baseline PGFM and amplitude and frequency of PGFM peaks in blood samples collected hourly on Day 18 did not differ between saline and oxytocin cycles. In Exp. II, 7 non-lactating Holstein cows were infused with saline or oxytocin from Day 13 to Day 25 after oestrus in a cross-over experimental design. Secretion of progesterone decreased from 6.8 +/- 0.7 ng/ml on Day 16 to less than 2 ng/ml on Day 22 of saline cycles; however, during oxytocin cycles, luteolysis did not occur until after Day 25 (P less than 0.05). Interoestrous interval was 5.9 days longer for oxytocin than for saline cycles (P less than 0.05). In blood samples taken every 2 h from Day 17 to Day 23, PGFM peak amplitude was higher (P less than 0.05) in saline (142.1 +/- 25.1 pg/ml) than in oxytocin cycles (109.8 +/- 15.2 pg/ml). Nevertheless, pulsatile secretion of PGFM was detected during 6 of 7 oxytocin cycles. In both experiments, the anticipated rise in serum oestradiol concentrations before oestrus, around Days 18-20, was observed during saline cycles, but during oxytocin cycles, concentrations of oestradiol remained at basal levels until after oxytocin infusion was discontinued. We concluded that continuous infusion of oxytocin caused extended oestrous cycles, prolonged the secretion of progesterone, and reduced the amplitude of PGFM pulses. Moreover, when oxytocin was infused, pulsatile secretion of PGFM was not abolished, but oestrogen secretion did not increase until oxytocin infusion stopped.     

The effects of steroid hormones and gonadotropins on in vitro placental conversion of pregnenolone to progesterone

Using human term placental mitochondrial preparations, optimal conversion of [3H]pregnenolone to [3H]progesterone was obtained at 30 min incubation and with a mitochondrial protein content of 2.5-3.5 mg/ml. Estradiol, estrone, progesterone and testosterone in a dose range of 0.03-8.66 mumol inhibited the in vitro conversion of [3H]pregnenolone to [3H]progesterone by placental homogenates. All four steroids inhibited the pregnenolone to progesterone conversion in a dose-dependent manner. The ID50 (dose required to inhibit conversion of pregnenolone to progesterone by 50%) was 0.04 mumol for estradiol, 0.13 mumol for testosterone, 0.3 mumol for progesterone and 1.0 mumol for estriol. Neither gonadotropin releasing hormone (50-1000 ng) nor human chorionic gonadotropin (5-500 IU) affected the placental basal conversion rate of pregnenolone to progesterone in vitro. Our findings indicate that steroid hormones such as estradiol, estrone, testosterone and progesterone can inhibit local placental progesterone biosynthesis through inhibition of the enzyme complex 5-ene-3 beta-hydroxysteroid dehydrogenase.     

Response of adult male rats to LH-RH after neonatal immunization with antiserum to LH-RH

Male rats were passively immunized at Day 5 of age with LH-RH antiserum. Their response to LH-RH at 100 days of age was examined. Serum FSH and LH concentrations increased more than in control rats, although basal plasma levels were similar. The pituitary content of LH, but not FSH, was significantly increased, and hypothalamic content of LH-RH was similar in both groups. The testes and seminal vesicles were smaller in experimental animals than in controls. It is suggested that transient blockade of LH-RH secretion during the neonatal period produces abnormalities in pituitary-testicular functon in the adult rat.     

Prepartum onset of maternal behavior in hamsters and the effects of estrogen and progesterone.

The onset of maternal behavior in pregnant hamsters was measured by presenting foster pups at 0900 and 2100 hr on Day 15 and at 0300, 0500, and 0700 hr on Day 16 and then at hourly intervals until parturition began. The occurrence of parturition was determined at each maternal test and at 0.5 hr intervals beginning at 0700 hr on Day 16. Nulliparous and primiparous animals became maternal at approximately the same time on Day 16, 2 and 6 hr prepartum, respectively, demonstrating that parturition is not essential for maternal behavior. The second experiment showed that nulliparous females injected with either 1 μg or 10 μgm estradiol-17β (E₂), 0.1 mgm progesterone (P), 10 μgm E₂ plus 0.1 mgm P, or oil at 1200 hr on Day 15 became maternal at the same time of day (0800–1000 hr) while parturition was delayed 8 hr in females receiving P. The results suggest a dissociation between the regulation of parturition and maternal care and are compared to previous research into the hormonal basis of maternal behavior in rats.