Maternal estrogen and progesterone levels after hypophysectomy in early pregnancy and in term fetuses or newborn monkeys

Pregnant rhesus monkeys ($\text{Macaca}$$\text{mulatta}$) were hypophysectomized at 8–10 weeks gestation to determine effects on plasma levels of estrone (E₁), estradiol-17β (E₂) and progesterone (P). The first group of monkeys was subsequently fetectomized At 107–114 days. After hypophysectomy there was an initial decrease in maternal peripheral plasma E₂ followed by a rise to preoperative levels within 4–5 weeks. Plasma levels of e₁ and P were not markedly altered. After fetectomy, peripheral estrogen concentrations, especially E₂, declined markedly. In the second experimental series, we have examined the effects of maternal hypophysectomy on levels of E₁, E₂ and P either (1) in both mother and newborn baby or (2) in mother, term fetus and umbilical vein. Groups of hypophysectomized and intact pregnant monkeys (3 each) were delivered by cesarean section at the expected time of parturition. Other hypophysectomized and intact monkeys (2 each) delivered normally. E₂ levels were elevated significantly in plasma of hypophysectomized monkeys at the time of cesarean delivery and in newborn babies of hypophysectomized mothers shortly after parturition. Except for these differences, the maternal hypophysis apparently is not a major factor in the control of E₁, E₂ and P concentrations in pregnant rhesus monkeys.     

Effects of fetectomy on plasma estrogens and progesterone in monkeys (Macaca mulatta)

Effects of fetectomy on peripheral plasma levels of estrogens and progesterone were studied at 10 weeks (3 monkeys) and 16 weeks gestation (4 monkeys). Fetectomy was followed by a decrease in maternal peripheral plasma estradiol 17-β (E₂) at a time when E₂ levels remained elevated in intact pregnant monkeys. Estrone (E₁) levels, initially low at fetectomy (10 weeks), were maintained at similar low levels in contrast to elevated concentrations observed in normal animals during the final 30 days of pregnancy. In the absence of the fetus, progesterone (P) levels were similar to those of the normal pregnancies. After removal or delivery of the placenta, P levels decreased rapidly. Maternal hypophysectomy in one animal (10 weeks) produced a transient decrease in E₂ followed by recovery to control levels by 16 weeks. Subsequent fetectomy (16 weeks) was followed by a precipitous decline in maternal E₂ levels. In conclusion, results indicate: a fetal origin, possibly from adrenal precursors, for the major contribution of E₂ during the last 3 months and E₁ during the last month of gestation; and placental production of most of the P found in peripheral plasma of pregnant rhesus monkeys.     

Excessive ovarian follicular development in pregnant pigtailed macaques (Macaca nemestrina)

To evaluate the status and possible control of ovarian follicular development during pregnancy, circulating levels of estrone (E₁), estradiol-17β (E₂), and follicle-stimulating hormone (FSH) were measured throughout gestation in both intact and ovariectomized pregnant pigtailed monkeys (Macaca nemestrina). From an additional group of pregnant monkeys, ovaries were obtained at late gestation (on day 150 or 159 of pregnancy) for histological studies. Circulating concentrations of E₁ and E₂ increased on day 13 and remained elevated for about 10 days; they then declined and reached low levels on day 32 of gestation. After day 60, there were gradual but smaller increases in estrogen levels to day 140, after which both E₁ and E₂ levels increased significantly, reaching maximum levels (E₁ = 832.2 ± 210.8 pg/ ml; E₂ = 1.66 ± 0.32 ng/ml) at the end of pregnancy. Removal of ovaries on day 35 of gestation did not affect pregnancy or the pattern of estrogen secretion. Serum concentrations of FSH demonstrated only minor fluctuations during pregnancy but were similar to those found during the early follicular phase of cycling pigtailed monkeys investigated in this study. Ovarian histology revealed extensive follicular growth; in addition to the corpus luteum of pregnancy, ovaries were packed with pre-antral, small antral, and medium-sized Graafian follicles. Some of these follicles appeared to be cystic and showed various degree of atresia; their general appearance was similar to the follicles of human females with polycystic ovary syndrome. Our data suggest that FSH may initiate ovarian follicular growth during gestation. High levels of estrogens were incapable of suppressing FSH secretion but may be responsible for the induction of atresia in a large number of follicles in pregnant pigtailed monkeys.     

Menopause in female rhesus monkeys

Fifteen female rhesus monkeys (Macaca mulatto), ranging in age from 8 to 34 years, were studied for one year to characterize the endocrine and menstrual changes associated with menopause in this species. Five monkeys were premenopausal; these younger monkeys, ages 8–11 years, menstruated and showed cyclic ovarian activity during the 12–month study period, as evidenced by menses and periodic elevations of serum estradiol (E₂) and luteinizing hormone (LH) concentrations. Four females, ages 24–26 years, were in transition to menopause. Two of these perimenopausal females menstruated and secreted E₂ and LH in a periodic fashion; the other two females showed elevated LH concentrations, consistently low E₂ levels, and no evidence of menstruation. Six females, ages 27–34 years, were clearly postmenopausal; LH concentrations were high, whereas E₂ concentrations were uniformly low. There was a significant inverse correlation between basal E₂ concentrations and age, and a significant positive correlation between age and LH concentrations across all 15 animals. Hormonal changes indicative of ovulation, when they occurred, were generally restricted to the winter and early spring months. Histological analysis of ovaries from four postmenopausal females revealed little or no evidence of active folliculogenesis. These data indicate that menopause in female rhesus monkeys does not occur until the second half of thethird decade of life. © 1995 Wiley-Liss, Inc.     

Effects of PGF2α and PGF2α, 1–15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey

The effects of prostaglandin (PG)F_2α and PGF_2α, 1–15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF_2α, 1–15 lactone were significantly (P <0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P <0.008) lower by the second day after the initial treatment with either PGF_2α or PGF_2α, 1–15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P <0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF_2α, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF_2α, 1–15 lactone. These data indicate that PGF_2α, 1–15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF_2α, 1–15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF_2α.     

Characterization of estrogen and progesterone receptors in monkey endometrium: methodology and effects of estradiol and/or progesterone on endometrium of castrate monkeys.

Appropriate methods for repeated surgical collection of endometrial tissue from rhesus monkeys, and characterization of cytosol and nuclear estrogen (E₂) and progesterone (P) receptors (R) are described. Tissue collection was made in the mid-luteal phase at abdominal fundal hysterotomy. Functional status of the ovaries was determined by visual inspection and RIA of E₂ and P in serum. Receptor assay procedures were devised permitting the measurement of total cytosol and nuclear receptor concentration. Sucrose density gradients of labelled cytosol were made and a 4S saturable binding component for ³H P and for ³H E₂ were found. Equilibrium dissociation constants of ³H E₂ and ³H R5020 were 2.1×10^?10M and 3.6 × 10^?9M, respectively. These binding characteristics are similar to those found in human endometrium and suggest that these surrogate primates have extensive utility in investigation of factors influencing E₂R and PR concentrations in endometrial tissue during the menstrual cycle and implantation. Simulated menstrual cycle were produced in 20 castrate monkeys by sequential treatment with estradiol and progesterone in silastic capsules. RIA of E₂ and P, and gonadotropins in peripheral serum provided assuredness of the hormonal status of each monkey under treatment. Cytosol and nuclear receptors for E₂ and P were measured in the endometrium after different intervals of the treatment. E₂ receptor (E₂R) levels were not changed during the estrogen sequence, but were lowered by progesterone therapy in both cytosol and nuclear components. Progesterone receptor (PR) synthesis in cytosol was induced by exogenous estrogen. The total concentration of PR decreased with the uptake of P by the cell; meanwhile, the ratio of cytosol to nuclear P receptors declined. These data suggest that this sequential estrogen-progesterone regimen induces the changes in E₂R and PR patterns in the endometrium of ovariectomized monkeys which occurs due to ovarian cyclicity in the normal menstrual cycle.     

Role of the primate placenta in cortisol secretion by the maternal adrenals

Peripheral serum cortisol levels were measured throughout gestation in 5 intact pregnant rhesus monkeys (Macaca mulatta) and 3 hypophysectomized-fetectomized monkeys, leaving the placentas in situ and viable. These monkeys, as well as 4 other groups used to separately control for effects of pregnancy, hypophysectomy, or fetectomy, were unilaterally (left) adrenalectomized to permit comparisons of adrenal gland weights. Circulating cortisol levels of intact pregnant monkeys tended to rise slightly with advancing gestation. However, hypophysectomy at 70 to 73 days after fertilization caused a marked decline (p < 0.01) in serum cortisol concentrations to about 1/2 the preoperative level. These monkeys were fetectomized at 107 to 114 days without further reduction in circulating cortisol levels. In hypophysectomized-fetectomized monkeys, either surgical removal of the placentas near term or abortion was followed by a rapid decrease in peripheral cortisol to undetectable concentrations. Their cortisol levels were 5 to 12 times higher in left adrenal venous effluent than in peripheral circulation on the day of placental delivery. The presence of a viable placenta protected against the extensive adrenocortical involution seen in nonpregnant hypophysectomized monkeys (p < 0.01). Fetectomy, alone or in combination with hypophysectomy, did not alter left adrenal gland weights from those of intact pregnant monkeys. Thus, continued cortisol secretion and maintenance of adrenal weight in hypophysectomized-fetectomized monkeys, in the presence of a functional placenta, supports the existence of a placental adrenocorticotropin in this primate.     

17 β-hydroxysteroid dehydrogenase in monkey endometrium during the menstrual cycle and at the time of implantation

In order to further identify physiological similarities between 17β-hydroxysteroid dehydrogenase (HSD) in human and monkey endometrium, and to evaluate the role of estradiol-17β (E₂) oxidation to estrone (E₁) during periimplantation events, 30 rhesus monkeys were studied at different intervals of the nonfertile menstrual cycle (days 8, 12, 15, 18 and 24). Also, five pregnant monkeys provided endometrial tissue on day 24 of the fertile menstrual cycle, near the expected time of implantation. HSD activity in endometrium was low at midfollicular phase (day 8), increased to maximal levels (8-fold) during the periovulatory span (days 12 and 15),and was intermediate in mid to late luteal phase (days 18 and 24) in non-fertile menstrual cycles. In the absence of ovulation, HSD was low throughout. These enzyme data fit with a pattern of daily peripheral serum levels of E₂ and progesterone (P) and suggest that when the normal sequence of P follows elevated estrogens in late follicular phase, HSD activity is markedly enhanced in the early luteal phase. However, HSD activity in endometrium did not increase more in the fertile menstrual cycle, despite further elevations of serum P during rescue of the corpus luteum.     

A study of prostaglandin F2α as the luteolysin in swine: V comparison of prostaglandin F, progestins, estrone and estradiol in uterine flushings from pregnant and nonpregnant gilts

Uterine flushings were collected from 38 gilts representing Days 6,8,10,12,14,15,16 and 18 of the estrous cycle and pregnancy. The same group of gilts were represented within each of the respective days of the estrous cycle and pregnancy, i.e., three to six gilts per day per status. Uterine flushings (about 40ml) were assayed for prostaglandin F (PGF), estrone (E₁), estradiol (E₂), progestins (P) and protein. Nonpregnant gilts had higher (P<.01) concentrations of P in uterine flushings than pregnant gilts, but pregnant gilts had higher (P<.01) E₁ and E₂ concentrations. Significant day by status interactions were detected for E₁ (P<.05), but not for E₂ concentrations in uterine flushings. Total recoverable PGF and PGF concentrations in uterine flushings were greater (P<.01) in pregnant than nonpregnant gilts and significant (P<.01) day by status interactions were detected. In nonpregnant gilts, PGF increased between Days 12 and 16, i.e., during the period of corpora lutea (CL) regression. In pregnant gilts, PGF in uterine flushings increased markedly between Days 10 and 18. Total recoverable PGF on Day 18 of the estrous cycle was only 464.5 ± 37.6 ng as compared to 22,688.1 ± 1772.4 ng on Day 18 of pregnancy. Total recoverable protein was also higher (P<.01) in pregnant gilts. These data indicate that PGF synthesis and secretion by the uterine endometrium and/or conceptuses is not inhibited during pregnancy and suggest that PGF is sequestered within the uterine lumen of pregnant gilts, as is the total protein component of endometrial secretions referred to as histotroph.     

Atretogenic action of estrogen in rhesus monkeys: Effects of repeated treatment

The effects of 17β-estradiol (E₂), administered in Silastic capsules for 24 hours at intervals of 10 or 14 days, on follicular development and menstrual cycle characteristics were studied in 13 rhesus monkeys. In seven monkeys receiving E₂ at l0-day intervals for 50 treatment periods, new follicles frequently developed between treatments but usually regressed. In seven instances, the follicles persisted longer than expected but were steroidogenically suppressed and regressed spontaneously. Ovulation occurred in only two instances. In six monkeys receiving E₂ at 14-day intervals, new follicles developed regularly, with seven ovulations occurring in 37 treatment periods. A persistent anovulatory follicle was noted in only one instance. Menstruation occurred with equal frequency, and the interval from treatment to onset of menstruation was not significantly different regardless of treatment or the occurrence of ovulation; the intervals between menstruation approximated those of normal menstrual cycles. In general, following termination of treatment, menstrual cycles returned to normal quickly. These data indicate that E₂ administered intermittently at 10-day intervals effectively suppresses ovulation, and they provide new insight into the actions of E₂ on folliculogenesis in primates.     

Patterns of estrogen and progesterone receptors in monkey endometrium during the normal menstrual cycle

Total concentrations of estradiol-17β (E₂) and progesterone (P) receptors (R) were measured in the endometrium of rhesus monkeys ($\text{Macaca mulatta}$) during the normal menstrual cycle. The endometrium was collected at abdominal fundal hysterotomy on days 8, 12, 15, 18 and 24 of the menstrual cycle. Visual inspection of the ovaries and measurement of E₂, P, follicle stimulating hormone (FSH) and luteinizing hormone (LH) provided assuredness of normal ovarian function. Exchange procedures were used in order to measure the total concentrations of E₂R and PR in nuclear and cytosol fractions. The pattern of estrogen receptor showed a slight increase in the cytosol and nuclear concentrations at the preovulatory interval. Later, the total E₂R concentration was decreased when P increased during the luteal phase. Cytosol PR synthesis was parallel to the serum E₂ increase during the late follicular phase. Secretion of P by the corpus luteum was accompanied by a rapid nuclear translocation and concomitant decrease in cytoplasmic PR. Thereafter the total PR concentration declined during the second half of the luteal phase. These findings in monkey endometrium are similar to those reported for human endometrium during the normal menstrual cycle and further establish the utility of these surrogate primates in investigations indicative of human endometrial function.     

Elevation of rhesus monkey plasma luteinizing hormone levels in response to E series prostaglandins

Experiments were carried out to assess the influence of prostaglandins (viz. PGE₁, PGE₂ and PGF_2α) on plasma concentrations of FSH and LH in the female rhesus monkey. Monkeys were ovariectomized and treated with estradiol benzoate to suppress endogenous gonadotropin levels prior to these experiments. Femoral venous blood was taken at intervals following a single carotid arterial injection of the PG in anesthetized monkeys. FSH and LH concentrations, determined by radioimmunoassay, were not significantly altered in 4 control animals receiving saline (2) or ethanol-saline (2), the vehicles for PGF_2α and for the E series PGs, respectively. PGE₁ (5mg) effected dramatic elevations of LH within 5 min in 3 animals and the high plasma concentrations were maintained at least for 60 min. Similarly, 5.0 mg of PGE₂ effected rapid elevation of LH concentrations, from 2- to 7-fold pre-injection levels in 3 animals. In contrast, FSH levels were not so markedly altered by PGE₁ and PGE₂, but in general, appeared to be somewhat decreased by these treatments. PGF_2α had no effect on plasma FSH and LH concentrations. These data demonstrate the ability of PGs of the E series to elevate plasma LH concentrations in the rhesus monkey and support studies in other species suggesting a modulating role for PGs on gonadotropin secretion or release.     

Extremely high circulating levels of 1α,25-dihydroxyvitamin D3 in the marmoset,a new world monkey

Compared to most mammals, the marmoset, a new world monkey, requires particularly large amounts of vitamin D to maintain normal growth. We compared serum concentrations of vitamin D metabolites in marmosets with rhesus monkeys and humans. The circulating levels of 1α,25-dihydroxyvitamin D₃ [1α,25(OH)₂D₃] in marmosets were 4 to 10 times higher than those in rhesus monkeys and humans. But none of the marmosets exhibited hypercalcemia. In two marmosets which had suffered bone fractures, the 1α,25-(OH)₂D₃ levels were particularly elevated. These results suggest that the marmoset has an end-organ resistance to 1α,25(OH)₂D₃.     

Luteolytic action of 15-keto prostaglandin F2α in the rhesus monkey

The naturally-occurring metabolite of prostaglandin F_2α, 15-keto prostaglandin F_2α (15-keto PGF_2α), elicited rapid and sustained declines in serum progesterone concentrations when administered to rhesus monkeys beginning on day 22 of normal menstrual cycles. Evidence for luteolysis of a more convincing nature was obtained in studies where a single dose of 15-keto PGF_2α was given on day 20 of ovulatory menstrual cycles in which intramuscular injections of hCG were also given on days 18–20; serum progesterone concentrations fell precipitously in monkeys within 24 hours following intramuscular administration of 15-keto PGF_2α. However, corpus luteum function was impaired in only 4 of 11 early pregnant monkeys when 15-keto PGF_2α was administered on days 30 and 31 from the last menses, a time when the ovary is essential for the maintenance of pregnancy. Gestation failed in 2 additional monkeys 32 and 60 days after treatment with 15-keto PGF_2α, but progressed in an apparently normal manner in the remaining 5 animals. Two pregnant monkeys treated with 15-keto PGF_2α on day 42 from the last menstrual period, a time when the ovary is no longer required for gestation, continued their pregnancies uneventfully. Corpus luteum function was not impaired in 9 control monkeys which received injections of vehicle or hCG at appropriate times during the menstrual cycle or pregnancy.     

Ovulation induction in rhesus monkeys by treatment with gonadotropins and prostaglandins

In rhesus monkeys (Macaca mulatta), superovulation has been successfully induced using a combined regimen of PMS, HCG and PG E₁ or E₂. The ovulation was confirmed by a number of ova recovered either from the tubes or from the uterine flushings at various intervals after ovulation. The time of ovulation in this study under the conditions cited appears to be around 60 hrs after HCG, 36 hrs after PG administration.     

Effects of PGF2alpha and PGF2alpha, 1-15 lactone on the corpus luteum and on early pregnancy in the rhesus monkey.

The effects of prostaglandin (PG)F2alpha and PGF2alpha, 1-15 lactone were compared in luteal phase, non-pregnant and in early pregnant rhesus monkeys. Animals treated with either PG after pretreatment with human chorionic gonadotropin (hCG) had peripheral plasma progesterone concentrations that were not statistically different from those in animals treated with hCG and vehicle. However, menstrual cycle lengths in monkeys treated with PGF2alpha, 1-15 lactone were significantly (P less than 0.02) shorter than those in vehicle treated animals. In the absence of hCG pretreatment, plasma progesterone concentrations were significantly (P less than 0.008) lower by the second day after the initial treatment with either PGF2alpha or PGF2alpha, 1-15 lactone than in vehicle treated monkeys. Menstrual cycle lengths in monkeys treated with either PG were significantly (P less than 0.04) shorter than those in animals treated with vehicle. There were no changes in plasma progesterone concentrations in early pregnant monkeys treated with PGF2alpha, and pregnancy was not interrupted. In contrast, plasma progesterone declined and pregnancy was terminated in 5 of 6 early pregnant monkeys treated with PGF2alpha, 1-15 lactone. These data indicate that PGF2alpha, 1-15 lactone decreases menstrual cycle lengths in non-pregnant rhesus monkeys. More importantly, PGF2alpha, 1-15 lactone terminates early pregnancy in the monkey at a dose which is less than an ineffective dose of PGF2alpha.     

Induction of atresia of the dominant follicle in rhesus monkeys (Macaca mulatta) by the local application of estradiol-17β

Estradiol-17β (E₂), administered systemically to rhesus monkeys during the follicular phase of the menstrual cycle, induces atretic changes in the microenvironment of the dominant follicle (DF), which results in its demise. It has been proposed that this effect of E₂ represents a direct action at the ovarian level. The present study was designed to test this hypothesis, using local treatment with E₂. After identification of the DF during laparoscopy on day 6 of the cycle, female monkeys were laparotomized and their ovaries exposed. Either corn oil (20 μl, controls) or E2 (100 μg ) in oil vehicle (experimentals) was injected into the ovary near the DF. In control animals, preovulatory release of gonadotropins and ovulation were normal in five of six animals, with cycle and luteal phase lengths of 27.8 ± 2.2 days and 14.6 ± 2.5 days, respectively (x? ± S.D.). Conversely, in only one of six animals in the experimental group did ovulation occur at the expected time (P < 0.05). In the other five treated animals, E₂ induced atresia of the DF and significantly extended cycles (35.4 ± 5.4 days) without affecting luteal phase lengths (12.0 ± 1.4 days). Concentrations of estrogen in peripheral sera of some animals were increased transiently at 6 h after injection of E₂ but returned to normal by 12 h; this duration of estrogen exposure is far less than the 24 h required to induce atresia of the DF in previous studies. At 6 h after injection of E₂, there was a statistical difference between controls and experimentals in concentrations of circulating estrogen; however, these changes were apparently not enough to alter pituitary secretion of follicle-stimulating hormone or luteinizing hormone. These data support the hypothesis that E₂ can induce atresia of the DF in rhesus monkeys by acting locally at the ovary.     

Confirmation of ovulation and characterization of luteinizing hormone and progesterone secretory patterns in cycling,isosexually housed Bolivian squirrel monkeys (Saimiri boliviensis boliviensis)

In the female Bolivian squirrel monkey a much greater elevation of serum estradiol (E₂) was measured after mating than that observed in similary cycling monkeys that did not mate. This raised the possibility that cycling squirrel monkeys may not ovulate during nonmated cycles To test this hypothesis, we performed laparoscopies on nine isosexually housed, cycling monkeys to observe the ovaries after the luteinizing hormone (LH) surge, which was measured by mouse interstitial cell bioassay using LER 1909-2 as the standard. Single ovulatory stigmas were identified as well demarcated, red, punctate depressions at the center of dome-shaped elevations on the ovarian surface in eight monkeys, when laparoscopically examined 9-56 hr after the LH peak. One monkey examined laparoscopically prior to the LH surge had a large translucent cystic follicle, confirming the morphology of the mature prevulatory follicle. Mean progesterone (P) concentrations fell to a nadir 1 day prior to the LH surge and then began to rise on the LH surge. Peak P levels were found 2 days after the LH surge. In the ovulating animals in which periovulatory E₂ levels were measured, no value was greater than 800 pg/ml, indicating that the presence of follicular rupture was not sufficient to account for the elevated E₂ levels observed after mating. These data confirm ovulation and follicular rupture in the absence of mating and delineate the relationship between periovulatory LH, P, and E₂ secretory patterns in cycling squirrel monkeys.     

The pituitary-gonadal axis before puberty: Effects of various estrogenic steroids in the ovariectomized rat

A series of experiments were conducted to determine the effects of several estrogens upon FSH and LH secretion in immature ovariectomized rats. Groups of animals were castrated at 26 days of age and treated for 5 days post-operatively with various dosages of one of the following steroids: estrad1ol-17β(E₂), estradiol benzoate (EB), estrone (E₁), equilenin (EQ), 17α-ethinyl estradiol (EE), or mestranol (ME). Uterine weights were recorded and blood taken for radioimmunoassay.Estradiol was able to suppress both FSH and LH within a “physiologic dosage range” (PDR), wherein both gonadotropins were suppressed to intact control levels by a dose which did not stimulate uterine weight higher than intact control weight. EB and ME suppressed LH but not FSH at the PDR; the other steroids suppressed at higher than PDR doses. LH was preferentially suppressed, as compared to FSH, by all 6 steroids. By biological potency the order of activity was E₂ = EE ? EB ? ME ? E₁ ? EQ. For relative ability to suppress FSH (compared to LH), the order was E₁ or E₂, ? ME ?EB ? EE ? EQ. At higher doses (near maximum uterine stimulation), e₁, E₂ and EE produced higher FSH and LH than suppressed levels seen at lower doses; a pharmacologie dosage of E₂ caused re-suppression of both gonadotropins.Results indicate that a feedback system is present before puberty and this system is sensitive to very low levels of estrogens. Likewise, there is a potential for positive feedback present for higher estrogen levels, and a complete suppression occurs at pharmacologie levels. There appears to be a significant discrepancy between the biologic activity (by uterine weight) of estrogens and their ability to affect gonadotropin     

Variables affecting the yield and developmental potential of embryos following superstimulation and in vitro fertilization in rhesus monkeys

Three follicular-stimulation protocols were compared to evaluate the yield and quality of oocytes obtained from rhesus monkeys. Five animals received a high-dose regimen of PMSG (protocol I), three received a lower-dose regimen (protocol II), and two received Clomid-Pergonal (protocol III). Oocytes were recovered at laparoscopy after HCG injection, fertilized in vitro, and cultured up to the blastocyst stage. Yields of mature oocytes were 17.2 ± 13.0 (80% of total recovered), 6.7 ± 6.6 (41%), and 4.5 ± 2.5 (90%) per stimulated cycle for protocols I, II, and III, respectively. Of mature oocytes, 72%, 45%, and 89% were fertilized for protocols I, II and III, respectively. Protocol I produced the most fertilized oocytes per stimulated cycle (11.6 ± 11.6) and the greatest E₂ production (approximately fourfold that maximally expected for an unstimulated cycle). For the combined protocol I and II results, there was a significant correlation (P ? 0.05) between mean embryo development score and E₂ production. Fertilized oocytes from protocol I yielded 7.8 ± 8.0 morulae and 6.8 ± 7.2 early zonal blastocysts per cycle. After transfer of nine singleton embryos to surrogate recipients, one live birth resulted. We conclude that our high-dose PMSG regimen offers the best means at present for obtaining susbstantial numbers of developmentally competent oocytes in rhesus monkeys and that more extensive use of rapid serum E₂ assays for monitoring both stimulated cycles and those of potential surrogate recipients could help to predict the success of in vitro fertilization and embryonic development following embryo transfer in rhesus monkeys.