Relationship between serum luteinizing hormone and estradiol in prepubertal boars

Effects of estradiol on serum luteinizing hormone (LH) were studied in prepubertal boars. In Exp. 1, 15-wk-old boars were given (iv) 50 mug estradiol, 1 mg testosterone or 1.5 ml ethanol. Estradiol (P<0.05) decreased LH over a 2.5-hr period, but testosterone did not. In Exp. 2, an estradiol implant reduced LH sample variance (P<0.01) while LH (547 +/- 96 vs 655 +/- 43 pg/ml) and estradiol (14.2 +/- 3.3 vs 18.4 +/- 1.0 pg/ml; control vs implant) were unchanged in 12-wk-old boars. Pulsatile LH releases (4.3 +/- 1.1 vs 3.0 +/- 0.4 pulses/pig/8 hr; control vs treated) and pulse amplitude (272 +/- 34 vs 305 +/- 40 pg/ml) were not affected. The implant tended to decrease serum testosterone (4.86 +/- 0.75 vs 7.66 +/- 1.51 ng/ml; P<0.10). In Exp. 3, LH was higher after zero implants than after four implants (279 +/- 7 vs 227 +/- 9 pg/ml; P<0.01), and LH after two implants was also higher than after four implants (263 +/- 7 pg/ml; P<0.01) in 14-wk-old boars in a Latin square design. Peak LH after 40 mug gonadotropin releasing hormone (GnRH) was less after two and four implants (1,100 +/- 126 and 960 +/- 167 pg/ml, respectively; P<0.01) than after zero implants (1,742 +/- 126 pg/ml). Slope of the first 20 min of LH response to GnRH was greater after zero implants (45.3 pg/min; P<0.05) than after either two or four implants (20.6 and 16.9 pg/min, respectively). Implant treatment decreased serum testosterone (P<0.025) but increased estradiol (P<0.10). Small changes in serum estradiol resulted in changes in LH. These changes in sample variance and mean LH were recognized by boars as different from normal because serum testosterone decreased. Changes in LH may result from estradiol's negative effect on pituitary responsiveness to endogenous GnRH because response to exogenous GnRH was depressed by estradiol.     

Effects of luteinizing hormone on luteal cell populations in hypophysectomized ewes

To examine the effect of purified LH on development and function of luteal cells, 27 ewes were assigned to: (1) hypophysectomy plus 2 micrograms ovine LH given i.v. at 4-h intervals from Days 5 to 12 of the oestrous cycle (oestrus = Day 0; Group H + LH; N = 7); (2) hypophysectomy with no LH replacement (Group N-LH; N = 6); (3) control (no hypophysectomy) plus LH replacement as in Group H + LH (Group S + LH; N = 7); (4) control with no LH treatment (Group S-LH; N = 7). Blood samples were collected at 4-h intervals throughout the experiment to monitor circulating concentrations of LH, cortisol and progesterone. On Day 12 of the oestrous cycle corpora lutea were collected and luteal progesterone concentrations, unoccupied receptors for LH and number and sizes of steroidogenic and non-steroidogenic luteal cell types were determined. Corpora lutea from ewes in Group H-LH were significantly smaller (P less than 0.05), had lower concentrations of progesterone, fewer LH receptors, fewer small luteal cells and fewer non-steroidogenic cells than did corpora lutea from ewes in Group S-LH. The number of large luteal cells was unaffected by hypophysectomy, but the sizes of large luteal cells, small luteal cells and fibroblasts were reduced. LH replacement in hypophysectomized ewes maintained luteal weight and the numbers of small steroidogenic and non-steroidogenic luteal cells at levels intermediate between those observed in ewes in Groups L-LH and S-LH. In Group H + LH ewes, luteal and serum concentrations of progesterone, numbers of luteal receptors for LH, and the sizes of all types of luteal cells were maintained. Numbers of small steroidogenic and non-steroidogenic cells were also increased by LH in hypophysectomized ewes. In Exp. II, 14 ewes were assigned to: (1) sham hypophysectomy with no LH replacement therapy (Group S-LH; N = 5); (2) sham hypophysectomy with 40 micrograms ovine LH given i.v. at 4-h intervals from Day 5 to Day 12 of the oestrous cycle (Group S + LH; N = 5); and (3) hypophysectomy plus LH replacement therapy (Group H + LH; N = 4). Experimental procedures were similar to those described for Exp. I. Treatment of hypophysectomized ewes with a larger dose of LH maintained luteal weight, serum and luteal progesterone concentrations and the numbers of steroidogenic and non-steroidogenic luteal cells at control levels.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanism of down regulation of luteinizing hormone receptors and steroidogenesis in corpora lutea

The mechanism of ‘down regulation’ of luteinizing hormone receptors was investigated in pseudopregnant rats using a modified radioimmunoassay capable of measuring endogenous tissue-bound hormone. Treatment of pseudopregnant animals with a desensitizing dose (desensitization treatment) of human chorionic gonadotropin resulted in a decrease in receptor concentration. This decrease was prevented if the animals were treated prior to the desensitization treatment with indomethacin, an inhibitor of prostaglandin biosynthesis, suggesting a role for prostaglandins in down regulation. The desensitization treatment resulted in a time-dependent decrease in subsequent responsiveness of the tissue to luteinizing hormone. Basal progesterone production rate was also decreased following desensitization. Total tissue cholesterol was found to be decreased following desensitization treatment, without any change in the ratio of free to esterified cholesterol. Mitochondrial cholesterol was significantly reduced and pregnenolone production by the mitochondria of desensitized corpora lutea was also markedly reduced. However, when cholesterol was added to the mitochondria of desensitized corpora lutea, pregnenolone production was increased, reaching values almost equal to that shown by the control mitochondria. These results show that decrease in the responsiveness following desensitization treatment is due to, besides receptor loss, decrease in tissue cholesterol, in particular mitochondrial cholesterol. The cholesterol side chain cleavage activity, although low, appears to be functionally intact; the low activity could be attributed to low levels of mitochondrial cholesterol.     

Methylation in bovine luteal cells as a regulator of luteinizing hormone action

Experiments were conducted to determine if methylation is a part of the mechanism by which luteinizing hormone (LH) and epinephrine stimulate progesterone production by dispersed bovine luteal cells. Corpora lutea (CL) were collected from 24 Holstein heifers on Day 10 of the estrous cycle and dispersed with collagenase. Net progesterone accumulation, representing total progesterone synthesized by 10(6) cells during a 2-h incubation was determined. Cells from 7 CL were treated with 0 and 5 ng LH, in the presence and absence of methylation inhibitor, S-adenosyl-homocysteine (SAH, 1 mM). LH-stimulated progesterone production was inhibited (P less than 0.05) in the presence of SAH(209 +/- 19 vs. 119 +/- 7 ng/10(6) cells). In the absence of LH, progesterone production was unaffected (87 +/- 22 vs. 68 +/- 28) by SAH. Cells from 4 CL were treated with 10 micrograms epinephrine or 10 micrograms isoproterenol with and without SAH. Both epinephrine and isoproterenol-stimulated progesterone production was inhibited (P less than 0.05) by the presence of SAH (204 +/- 24 vs. 125 +/- 18 and 198 +/- 15 vs. 130 +/- 8). Progesterone production by cells from 4 CL was unaffected by the presence of SAH when treated with Medium 199 (M199) (75 +/- 32), 10 micrograms cholera toxin, which directly stimulates adenylate cyclase on the cytoplasmic side of plasma membranes (168 +/- 19), or 3 mM dibutyryl cAMP (210 +/- 40).(ABSTRACT TRUNCATED AT 250 WORDS)     

Suppression of luteal function in dogs by luteinizing hormone antiserum and by bromocriptine

Beagle bitches were treated with equine anti-LH serum (ALHS) or the dopamine agonist bromocriptine at selected times during the 2-month luteal phase of the ovarian cycle or pregnancy. After a single injection of ALHS (10 ml, i.m.) at Day 42 of pregnancy (N = 2) or the ovarian cycle (N = 3), progesterone was reduced (P less than 0.05) to 7-24% of preinjection values within 1-2 days, and by 4-8 days returned to levels not different from those in control bitches treated with normal horse serum. Injections of bromocriptine (0.1 mg/kg, i.m.) daily for 6 days caused abrupt declines in progesterone which lasted 6-8 days in bitches treated at Day 8 or 22 of pregnancy (N = 5). In bitches treated at Day 42 of pregnancy (N = 3) or in non-pregnant cycles (N = 4) the bromocriptine treatment caused declines (P less than 0.05) in progesterone which were permanent, extensive (less than 2 ng/ml), and therefore abortive. The declines in progesterone in response to immunoneutralization of LH and to prolactin-lowering doses of a dopamine agonist demonstrate that normal luteal function in dogs requires both LH and prolactin.     

In vitro effects of cycloheximide and luteinizing hormone on the estradiol-to-progesterone shift in follicular steroidogenesis

The objectives of this study were to establish a completely in vitro system that would simulate the in vivo effects of cycloheximide (cyclo) on preovulatory serum levels of estradiol (E2) (prolonged) and progesterone (P4) (reduced). Graafian follicles were removed from proestrous hamsters at 0900 h and incubated for a basal hour (Hour 1) with various doses of cyclo before the medium was replaced; in Hour 2, 100 ng luteinizing hormone (LH) was added with cyclo added every hour for 5 or 6 h. The endpoints were steroid levels/follicle/h per ml medium of P4, 17 alpha-hydroxyprogesterone (170HP), androstenedione (A), and E2. The goal was best accomplished with hourly addition of 400 ng cyclo, which reduced follicular protein synthesis by 76%. Cyclo suppressed P4 and 170HP and prolonged the accumulation of A and E2, in Hour 5 and Hour 6, correlated with sustained thecal C-17,20-lyase/17 alpha-hydroxylase as determined by enzyme assays. Cyclo therefore prevented the early demise of the enzyme complex after LH stimulation and hence prolonged the ability of the theca to provide androgens for conversion to E2 by the granulosa cells. Our earlier work established that one of the major effects of LH is to recruit the granulosa compartment as a source of C-21 steroids, and cyclo interferes with the availability of cholesterol to mitochondrial side-chain cleavage (Greenwald and Limback, 1984). Thus, cyclo affects follicular steroidogenesis through different mechanisms in theca and granulosa.     

Pattern of circulating luteinizing hormone isoforms during the estrous and luteal phases in Holstein heifers

The pattern of distribution of circulating luteinizing hormone (LH) isoforms in cattle during estrus and the luteal phase was investigated. In each stage, the stage of the estrous cycle was synchronized in seven Holstein heifers with a prostaglandin analogue. After estrus was detected, blood samples were taken at 2-h intervals for 24h. In the luteal phase, animals received 250 microg i.v. of GnRH and blood samples were collected every 15 min for 5h. LH concentration in the samples was determined. Samples with the greatest LH concentration in estrus (pre-ovulatory peak) and those collected 60 min after GnRH administration (luteal phase) were analyzed by chromatofocusing, eluted with a pH gradient from 10.5 to 3.5. Eluted LH was grouped into basic (pH > or = 7.5), neutral (pH 7.4-6.5) and acidic isoforms (pH < or = 6.4) as well as by pH unit. In both phases, basic forms were the most abundant, and these were greater (P < 0.05) during the luteal phase (78.4 +/- 4.2%) as compared with during estrus (57.1 +/- 6.2%); the proportion of neutral and acidic isoforms in estrus (13.7 +/- 2.6%; 28.5 +/- 2.8%) was greater (P < 0.05) as compared with the luteal phase (3.0 +/- 0.7; 18.7 +/- 3.4). These results indicate that the relative proportion of LH isoforms secreted by the adenohypophysis differ by stage of estrous cycle. The addition of excess of NaCl to the column modifies the antigen-antibody binding in the RIA, and the proteins eluted are erroneously quantified as LH; this is an artifact of the technique.     

Regulation of ovarian steroidogenesis in vitro by follicle-stimulating hormone and luteinizing hormone during sexual maturation in salmonid fish

The regulation of ovarian steroidogenesis in vitro by coho salmon FSH and LH was investigated in intact coho salmon follicles and isolated follicular layers at various stages of oocyte maturation, from late vitellogenesis until the completion of germinal vesicle breakdown (GVBD). In granulosa layers from all stages, LH, but not FSH, stimulated 17alpha,20beta-dihydroxy-4-pregnen-3-one (17, 20beta-P) production. In theca-interstitial layers from all stages, FSH and LH stimulated steroid production, LH being more potent than FSH. The basal steroid output of intact follicles was significantly lower than that of isolated follicular layers, and their response to FSH and LH also differed. First, the intact follicles produced 17alpha-hydroxyprogesterone in response to FSH during the central germinal vesicle stage while theca-interstitial layers did not. Second, estradiol-17beta production was not inhibited by LH during final oocyte maturation in intact follicles, as observed for granulosa layers. Our results indicate that LH is the determining factor regulating the production of the maturation-inducing steroid, 17,20beta-P, and the induction of GVBD in the salmonid ovary. In summary, we have provided evidence for maturation-associated changes in the effects of FSH and LH in the salmonid ovary, which further supports the hypothesis that FSH and LH have distinct functions in the teleost ovary.     

Relationship between testosterone, fluid content and luteinizing hormone receptors in the rat testis.

Injection of immature male rats with human chorionic gonadotrophin resulted in a decreased ability of the testis to bind [¹²⁵I]-labelled human chorionic gonadotrophin $\text{in vitro}$, and a marked, but transient increase in testis weight; the latter was apparently due to the accumulation of fluid containing high levels of testosterone. Intra-testicular injection of cycloheximide significantly inhibited all these changes, thus demonstrating their dependence on protein synthesis. It is concluded from this and other data that either testosterone itself or a steroidogenic protein intermediary may be responsible for the gonadotrophin-induced reduction in availability of gonadotrophin receptors.     

Splenic macrophages enhance prolactin and luteinizing hormone action in rat luteal cell cultures.

We have reported that splenic macrophages play a role in the regulation of progestin secretion in rats. In this study, splenic macrophages were obtained from cycling rats at different estrous cycle stages and co-cultured with luteal cells from mid-pseudopregnant rats in the absence/presence of prolactin (PRL) or luteinizing hormone (LH). The effect of macrophages on the luteotropic action of PRL and LH was evaluated with 2 parameters, i.e. an increase in total progestin output (progesterone plus 20 alpha-hydroxyprgn-4-en-one [20 alpha-OHP]), and an increase in the progesterone to 20 alpha-OHP (P/20 alpha-OHP) secretion ratio. Splenic macrophages obtained from proestrous or metestrous rats enhanced the PRL action to increase the P/20 alpha-OHP secretion ratio, but those from estrous or diestrous donors did not. Only macrophages from proestrous donors enhanced the PRL action to increase the total progestin output. In contrast, the LH action increasing the P/20 alpha-OHP secretion ratio was enhanced by splenic macrophages regardless of the donors' estrous cycle stages. The LH action increasing the total progestin output was enhanced only by proestrous or metestrous macrophages. Therefore, if luteal cells are co-cultured with proestrous macrophages, the luteotropic actions of PRL and LH can be fully expressed. These results indicate that splenic macrophages directly act on luteal cells and enhance the luteotropic action of PRL and LH, and that this function of splenic macrophages is modified somehow according to the donors' estrous cycle stages.     

Alterations in gonadal steroidogenesis in individuals expressing a common genetic variant of luteinizing hormone

Some pathologies of the pituitary-gonadal function have recently been found to be due to mutations of the gonadotropin or gonadotropin receptor genes. Although these conditions are extremely rare, they are very informative, by elucidating some less well characterized facets of normal gonadotropin function and the molecular pathogenesis of disturbances in sexual differentiation and fertility. In contrast, there is a common polymorphism in the Luteinizing Hormone (LH) β-subunit gene, where two point mutations cause two alterations in the amino acid sequence (Trp⁸→Arg and Ile¹⁵→Thr) and introduce an extra glycosylation signal to Asn¹³. The carriers of this variant gene are largely healthy, but certain mild differences in their gonadal function have been found, as reflected by alterations in gonadal steroidogenesis, pubertal development and predisposition to diseases such as infertility, polycystic ovarian syndrome, and breast and prostatic cancer. The purpose of this chapter is to review the current knowledge of the occurrence, special functional features and clinical correlates of this LH variant.     

Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep

Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin-treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low-affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of small luteal cells without a significant change in luteal mass by Day 3 and, overall, have fewer low-affinity PGF-2 alpha binding sites.     

Duration and amplitude of the luteal phase progesterone increment times the estradiol-induced luteinizing hormone surge in ewes

Progesterone (P) powerfully inhibits the neuroendocrine reproductive axis, but the mechanisms and site or sites of action of this steroid remain poorly understood. Progesterone exposure during the luteal phase also alters the responsiveness of the hypothalamus to increased concentrations of estrogen (E) during the follicular phase. Using an ovariectomized ovine follicular phase model, we investigated whether the amplitude and duration of the luteal phase increase in circulating P affects the E-induced surge in LH. Treatment of ewes for 10 days with two, one, or half an intravaginal P-releasing implant or with an empty implant demonstrated that P concentrations significantly (P: < 0.0001) delayed the time to surge onset upon exposure to an equal concentration of E. This delay was not due to a time-related difference in responsiveness to E after P clearance because the time of surge onset was not different when E treatment began 6, 12, or 24 h after the withdrawal of two P implants that had been present for 10 days. The final study demonstrated that the duration of P before treatment (5, 10, or 30 days) significantly (P: < 0.0001) delayed the responsiveness of the estradiol-dependent surge-generating system. There was no effect on surge amplitude or duration in any experiment. Thus, the amplitude and duration of exposure to luteal phase P significantly affect the neural elements targeted by E to induce the preovulatory LH surge.     

Regulation of follicular luteinization by a gonadotropin-releasing hormone agonist: Relationship between steroidogenesis and apoptosis

The purpose of this study was to evaluate the effects of GnRH-analog (Leuprolide acetate, LA) administration on follicular luteinization in equine chorionic gonadotropin plus human chorionic gonadotropin (eCG + hCG)-superovulated prepubertal treated rats. Results indicate that LA treatment decreases circulating levels of progesterone (P) and P accumulation in collagenase-dispersed ovarian cell cultures, though estradiol(E₂) production is increased. These data suggest that cells from the LA group may be less luteinized following gonadotropin treatment. Studies performed on histological ovarian sections after different times of eCG administration showed that LA injections produce lower amounts of corpora lutea and antral follicles, and a greater number of atretic and preantral follicles. The basal and LH-stimulated P and progestagen accumulations are decreased in incubations of corpora lutea isolated from the LA group. In addition, the mitochondrial cholesterol side-chain cleavage (P450_SCC) levels in corpora lutea from LA-treated rats are reduced, indicating that the decrease in P production observed is due in part to an alteration in the steroidogenic luteal capability. Immunocytochemical localization of nuclei exhibiting DNA fragmentation by the technique of terminal deoxynucleotidyl transferase end-labeling showed that LA treatment causes an increase in the number of apoptotic cells in preantral and antral follicles at all times studied (1, 2, 4, or 7 days of LA administration). A similar effect, though less pronounced, was observed in corpora lutea. It is concluded that LA treatment produces a failure in the steroidogenic luteal capability and an increase of apoptotic mechanisms in the ovary, producing as a consequence an interference in the follicular recruitment, growth, and luteinization induced by gonadotropins. Mol. Reprod. Dev. 51:287–294, 1998. © 1998 Wiley-Liss, Inc.     

Rapid decreases in phosphatidylinositol in isolated luteal plasma membranes after stimulation by luteinizing hormone

Phospholipid concentrations were determined in plasma membrane preparations from porcine corpora lutea after incubation for 15 to 120 s without or with 0.5 microgram/ml luteinizing hormone (LH) or 2 microM dibutyryl cyclic adenosine 3',5'-monophosphate (dbcAMP). Treatment with LH caused a dramatic loss of 9 nmol in plasma membrane phosphatidylinositol (PI)/mg protein after 15 s of incubation, but no significant changes in other measurable phospholipids. Also, phospholipid concentrations were unchanged in untreated and dbcAMP-treated plasma membranes. The nature of the LH-induced decrease in PI was studied by incubating plasma membrane preparations for 15 s with [gamma 32P] adenosine 3',5'-triphosphate (ATP). 32P was incorporated only into three phospholipids: phosphatidic acid, phosphatidylinositol 4'-phosphate (PIP), and phosphatidylinositol 4',5'-bisphosphate (PIP2). Although LH generated small but significant increases in labeling of PIP and PIP2, less than 0.5 nmol of total phospholipids/mg protein were radiolabeled in 15 s. Phosphatidylinositol kinase activity, the enzyme that converts PI into PIP, was not affected by LH or dbcAMP treatment. However, incubation of luteal plasma membranes for 15 s with LH resulted in an increase of approximately 2 nmol 1,2-diacylglycerol/mg protein more than that observed in untreated or dbcAMP-treated plasma membranes. In summary, these experiments suggest that LH may stimulate hydrolysis of PI (and possibly PIP and PIP2) in isolated luteal plasma membranes.     

Direct effect of the luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH on rat ovarian steroidogenesis

The luteinizing hormone releasing hormone analog D-Trp6-Pro9-Net-LHRH (LHRHa) inhibits rat ovarian estradiol secretion. To determine whether LHRHa decreases serum estradiol concentrations solely by inhibiting gonadotropin secretion or, in addition, by influencing directly ovarian estradiol biosynthesis, we examined the effects of LHRHa on the activities of 5 key ovarian steroidogenic enzymes. Fifty hypophysectomized, gonadotropin-treated rats were given either LHRHa (1 microgram/day) or saline sc during 7 days. The LHRHa treated animals exhibited a significant decrease in serum estradiol when compared with the control group (461 +/- 30 vs 31 +/- 5 pg/ml, mean +/- SE, P less than 0.001). The changes in estradiol concentration were associated with decreases in ovarian weight (372 +/- 19 vs 185 +/- 11 mg, P less than 0.001) and in the microsomal enzyme activities of 3 beta-hydroxysteroid dehydrogenase (156 +/- 5 vs 53 +/- 4 nmol/mg prot/min, P less than 0.001), 17 hydroxylase (4.7 +/- 0.8 vs 3.7 +/- 0.7 nmol/mg prot/min, P less than 0.002), 17,20 desmolase (279 +/- 14 vs 50 +/- 7 pmol/mg prot/min, P less than 0.001), 17 keto-steroid reductase (132 +/- 11 vs 6 +/- 1 nmol/mg prot/min, P less than 0.001), and aromatase (19 +/- 1.5 vs 0.9 +/- 0.1 nmol/mg prot/min, P less than 0.001) in LHRHa treated animals. These findings indicate that LHRHa can inhibit directly rat ovarian estradiol biosynthesis.     

Placental and luteal steroidogenesis in the pregnant rhesus monkey.

Progesterone, 20alpha-dihydroprogesterone, estrone and estradiol-17beta concentrations were estimated by radioimmunoassay in blood plasma from uterine, uteroovarian and femoral veins of rhesus monkeys (Macaca mulatta) on days 22, 49, 128 and 160 of gestation. Steroids were consistently more concentrated in uterine and uteroovarian that in femoral venous plasma and in many cases levels in the uteroovarian vein were also higher than those in the uterine vein indicating luteal secretion of both progestins and estrogens thoughout gestation. In some animals, however, the corpus luteum appeared quiescent. As reflected in the decline in the uterine venous progesterone/estradiol-17beta concentration ratio, a shift in steroid contribution from the uterus and its contents occurred between days 22 and 49 of gestation with progesterone declining more rapidly than estradiol-17beta. Progesterone/20alpha-dihydroprogesterone was higher in both uterine and uteroovarian than in femoral venous plasma suggesting peripheral metabolism of progesterone to 20alpha-dihydroprogesterone.