Induction of follicle-stimulating hormone (FSH) receptors in rat ovaries by estrogen priming.

Estrogen pretreatment of hypophysectomized immature rats stimulated granulosa cell proliferation and enhanced FSH binding to the ovary in vivo. The present studies were undertaken to ascertain whether estrogen pretreatment altered the number of specific FSH receptor sites per ovarian cell, resulting in increased FSH binding. Cell suspensions were prepared from the ovaries of groups of rats pretreated with graded doses of 17beta-estradiol. The isolated cells contained specific FSH receptors with high affinity for FSH. The results of these studies clearly showed that the number of specific FSH receptors per ovarian cell was unaffected by pretreatment with graded doses of 17beta-estradiol or with diethylstilbestrol. The enhanced in vivo FSH binding was solely the result of estrogen-induced proliferation of granulosa cells with a fixed number of specific FSH receptors per cell.

Metabolism of luteinizing hormone by the pseudopregnant rat ovary.

Ovarian metabolism of highly purified human LH (hLH) was studied in pseudopregnant rats. The animals were injected with 1.0 microgram (11.1 IU) hLH, iv, and groups of animals were killed between 15 and 300 min. The hLH present in ovarian cytosol and sera and eluted from ovarian membrane was determined by RIA. Ovarian membrane-bound LH increased rapidly for 1 h, after which it plateaued and then decreased 4 h after the injection. Cytosolic LH peaked at 1 h, but concentrations declined thereafter. When ovarian cytosol obtained from rats injected with 10 micrograms hLH was chromatographed on a Sephadex G-100 column, the major immunoreactive fraction cochromatographed with the LH used for injection. Cytosol harvested 15 min after LH stimulation contained a small peak which coeluted with LH alpha. No LH beta was detected. No evidence for extensive dissociation of the LH subunits was found. When hLH present in serum and ovarian cytosol or bound to ovarian membrane was chromatographed on Concanavalin A-Sepharose, different patterns of binding and elution with that lectin were observed and were consistent with differential modification of the oligosaccharide side chains of LH present in serum and associated with the ovary. The biological to immunological ratio of cytosolic LH decreased from 1.7 15 min after LH injection to 0.8 at 5 h. Compared to our previous studies with hCG, LH was metabolized more rapidly. Whether that difference in the rates of ovarian metabolism of the two gonadotropins contributes to the marked disparity in their quantitative biochemical effects induced by those hormones should be examined.

Differential subcellular distribution of bioactive human chorionic gonadotropin in pseudopregnant rat ovary.

The subcellular metabolism of internalized hCG was examined by monitoring the distribution of bioactive and immunoreactive hCG in subcellular fractions of pseudopregnant rat ovaries. Homogenates of ovaries from rats injected with 1.0 microgram (12.8 IU; bioassay) hCG were fractionated on self-generating Percoll gradients into three hCG-containing compartments: soluble proteins (cytosolic fraction), a combined plasma membrane/prelysosomal vesicle fraction, and lysosomes. The hCG level in each fraction was measured by RIA and in vitro bioassay. When necessary, receptor-bound hCG was dissociated at low pH before assay. Levels of cytosolic hCG were highest 1-3 h after injection, attaining peak immunoreactive concentrations of 18 ng/ovarian pair. Cytosolic hormone was not primarily derived from nonspecific trapping of serum or interstitial fluid, because after 1.0 microgram [125I]iodobovine gamma-globulin was injected into rats, cytosolic globulin levels (nanograms per ovarian pair) were approximately 7-10 times lower than those of hCG. Cytosolic hCG retained significant bioactivity for at least 10 h after hCG stimulation. Peak immunoreactive hCG levels associated with the plasma membrane/prelysosomal fraction were 82 ng/ovarian pair between 3 and 6 h after hCG injection, and hormone associated with that fraction retained the highest bioactivity of the three fractions examined. Peak lysosomal hCG levels reached 55 ng/ovarian pair 10 and 14 h after hCG stimulation, but lysosomal hCG was not bioactive. These results suggest that the lysosomal compartment is a major pathway for hCG inactivation. A nonlysosomal pathway for hCG inactivation may exist, because the cytosolic compartment contained partially inactivated hormone that did not appear to be of lysosomal origin. Cytosolic hCG may reflect hormone delivered to the cell cytoplasm or to the extracellular fluid that is either modified within prelysosomal vesicles or is degraded subsequently by nonlysosomal proteases.

New evidence for an acute role of protein kinase in hCG action.

The present experiments were designed to study whether exogenous hCG could elicit acute changes in the ovarian concentration of soluble cAMP-dependent protein kinases temporally related to binding of hCG and intracellular accumulation of cAMP. Cyclic AMP dependent protein kinase activity decreased five-fold within 5 to 30 min after intravenous administration of highly purified hCG to pseudopregnant rats. Moreover cAMP dependent protein kinase activity was totally suppressed with 0.5 IU hCG, whereas tissue concentration of cAMP continued to increase throughout the dose range (0.05-5.0 IU) of hCG used in the present studies. A marked fall in cAMP-dependent protein kinase activity had occurred before there was a significant change in intracellular accumulation of cAMP, possibly reflecting intracellular compartmentalization of cAMP. Inhibitors of protein did not affect the hCG-induced changes in tissue concentrations of cAMP and soluble cAMP dependent protein kinase activity but did suppress the recovery of cAMP dependent protein kinase activity to pretreatment levels. Cyclic AMP dependent protein kinases appear to play a significant role in mediating hormonal action in vivo. In addition the present studies suggest that, protein kinases may protect the cell from excessive hormonal stimulation.

Fate of human chorionic gonadotropin bound to rat corpora lutea.

The current studies were designed to ascertain the fate of hCG bound to rat corpora luteal cell receptors. Graded doses of highly purified hCG (CR119), ranging from 0.1-10.1 micrograms, were injected. Groups of pseudopregnant rats received iodinated hCG, unlabeled hCG, or both. Supraphysiological levels of hCG were used to enhance the internalization of hCG and its receptors. When ovarian membrane pellets (48,000 X g) were subjected to continuous sucrose density ultracentrifugation, two different ovarian membrane fractions (F1 and F2) bound hCG. Although an increase in hCG binding to the F2 membrane fraction was observed between 1-6 h after a single 0.1-microgram [125I]iodo-hCG injection, no subsequent enhanced binding to that fraction was observed. However, the F1 fraction bound at least 3 fold more hCG than did the F2 fraction 1, 6, 12, and 24 h after the injection of 0.1 micrograms [125I]iodo-hCG. When groups of animals were injected with 0.1, 1.0, or 10.0 micrograms unlabeled highly purified hCG, peak serum, ovarian plasma membrane, and ovarian intracellular hCG concentrations were observed at different times after hormone injection and suggested the progressive transfer of hCG from serum to ovarian fractions in a time- and dose-dependent relationship. Although no intracellular hCG was detected until 60 min after the single 0.1-microgram injection of hCG, both serum and membrane-bound levels were measurable within 15 min of that injection. From these observations, we suggest that ovarian intracellular hCG does not reflect significant contamination with serum or interstitial fluid or from significant dissociation of membrane-bound hCG during tissue handling. Finally, when intracellular hCG was subjected to continuous sucrose density gradient ultracentrifugation, a single major 135I peak was observed, and this comigrated with [125I]iodo-hCG. Our interpretation of the foregoing observations is that the major intracellular form of hCG is not receptor bound.

Hypothalamic-pituitary control of perinatal prolactin secretion in Macaca mulatta.

Sequential changes in maternal and fetal plasma and amniotic fluid concentrations of prolactin (PRL) and growth hormone (GH) were examined after these intravascular administration of thyrotropin releasing hormone (TRH) or L-dopa alone or combined directly to the near-term Rhesus fetus. The neonatal plasma responses to these same stimuli were also examined. Fetal and neonatal plasma PRL levels increased immediately after TRH injection and remained elevated from baseline levels (102-800%) throughout the 45 min sampling period. Maternal plasma PRL levels also increased markedly. Although amniotic fluid concentrations were more variable, the trend was an increase. After L-dopa injection, fetal and neonatal plasma PRL values declined 26-62% from baseline levels. Maternal plasma PRL concentrations also declined 30-50%, but amniotic fluid PRL concentrations progressively increased. When L-dopa and TRH were administered together, fetal plasma PRL levels declined 14-40% from initial levels, but maternal plasma PRL levels did not change in a consistent manner, and amniotic fluid PRL levels remained stable. There was no change from baseline fetal or neonatal plasma GH concentrations in these experiments. The plasma PRL responses of the primate conceptus to these stimuli are consistent with those found in the adult; the unresponsiveness of plasma GH is not. The direction and magnitude of changes in both maternal plasma and amniotic fluid PRL concentrations provide indirect evidence of placental transfer of TRH and L-dopa in some experiments, and require a biophysical explanation not apparent in others.

Structure of the human chorionic gonadotropin beta-subunit fragment from pregnancy urine.

A major portion of the hCG immunoreactivity detectable in pregnancy urine is derived from a fragment of hCG beta. This lacks the COOH-terminal portion of hCG beta, but retains immunoreactivity with most antibodies raised against the beta-subunit of hCG. To improve clinical measurements of hCG and assess the importance of such fragments in human urine, we have isolated and determined the structure of this molecule. The hCG beta fragment was isolated from a partially purified commercial preparation of hCG (Organon) by gel filtration and immunoaffinity chromatography using monoclonal antibodies. It was found to consist of two polypeptide chains composed of residues beta-(6-40) disulfide-bridged to residues beta-(55-92). It also differs from the beta-subunit of hCG in its carbohydrate structure, lacking sialic acid and having a low but variable amount of galactose. A beta-fragment containing the same two NH2-terminal sequences was also isolated from a single pregnant woman's urine. The two major polypeptides comprising the beta-fragment contain a total of nine half-cystine residues, raising the possibility that a free thiol may exist or that a third undetected disulfide-bridged peptide is present in the intact fragment. However, tests for the presence of a free thiol have been negative. Another intrinsic characteristic of the beta-fragment is the formation of a variable amount of dimer in solutions of neutral pH. beta-fragment will not combine with intact alpha-subunit. Despite the absence of regions beta-(1-5), beta-(41-54), and beta-(93-145), the beta fragment is recognized by the SB-6 antibody and most monoclonal antibodies elicited to the beta-subunit, thus excluding half of the amino acids of the beta-subunit from the epitope(s) where these antibodies bind.

A new radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles.

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75% macaque luteinizing hormone (mLH) and 1% mFSH, was used to demonstrate the specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone. The follicular phase of the menstrual cycle was characterized by continuously decreasing serum concentrations of mFSH, reaching a preovulatory nadir 48 h prior to the midcycle mFSH and mLH surges. Serum mFSH concentrations following the midcycle gonadotropin surges decreased progressively as serum progesterone concentrations increased and reached a plateau, and then increased during the last week of the menstrual cycle as corpus luteum function was waning. We have prepared a large pool of antiserum for distribution under the aegis of the Contraceptive Development Branch of the Center for Population Research, the National Institute of Child Health and Human Development.

Evidence for altered synthesis of human chorionic gonadotropin in gestational trophoblastic tumors.

Tissue extracts of molar tissue or choriocarcinoma, blood, or urine of 21 women with gestational trophoblastic disease were analyzed for hCG and its subunits. The extracts or biologic fluids were initially chromatographed through a standardized Sephadex G-100 column. Each fraction was radioimmunoassayed in homologous hCG, hCGalpha, and hCGbeta assays. Extracts of four hydatidiform moles contained primarily hCG but no free alpha subunit of that hormone. One of the molar extracts contained a small amount of free hCGbeta not observed in the small amount of free hCGbeta not observed in the extracts of the other three moles. Plasma and urine samples from 18 women with localized or metastatic gestational trophoblastic disease contained hCG but no free alpha or beta subunits; the neoplasms of those patients readily responded to chemotherapy, and all patients have had no evidence of disease for at least one year. The major portion of immunologic hCG present in the biologic samples was indistinguishable from native hCG in its physical behavior on Sephadex G-100 chromatography. On the other hand, three women with widely metastatic tumors died in spite of extensive chemotherapy. Extracts of tumors from two of those patients contained hCG and free subunits of hCG. The urine and plasma of the third patient contained hCG and hCGalpha with the concentration of hCGalpha far exceeding that for hCG in urine. The results of these studies clearly show a disparity between the forms of hCG found in the normal placenta and pregnancy sera, as previously reported, and those found in the neoplastic trophoblast with varying degrees of anaplasia. The most striking finding was the absence of free circulating hCGalpha in the sera in patients with gestational trophoblastic disease which responded to chemotherapy, since free hCGalpha is readily detectable in the sera of normally pregnant women.

Effect of dopamine on gonadotropin-releasing hormone-induced gonadotropin secretion in postmenopausal women.

Five healthy women who had previously undergone spontaneous menopause and had not received exogenous estrogens were studied with infusions of synthetic GnRH and dopamine to ascertain the site of dopaminergic modulation of pituitary gonadotropin secretion. Infusion of dopamine at 4 micrograms/kg . min for 5 h induced a significant decrease in circulating LH concentrations, but not those of FSH. LH levels returned to baseline concentrations during the postinfusion period. Infusion with synthetic GnRH at 10 micrograms/h for 5 h induced a biphasic change in circulating gonadotropin levels. When dopamine and GnRH were simultaneously infused for 5 h, FSH and LH responses were not statistically different from those observed when GnRH was infused alone. We conclude that in normal postmenopausal women, dopamine modulates pituitary gonadotropin secretion by affecting GnRH-secreting neurons in the median eminence and possibly at other hypothalamic sites.

Appearance of hCG in pregnancy plasma following the initiation of implantation of the blastocyst.

Plasma chorionic gonadotropin levels were measured by three different assay methods during early pregnancy in four patients following induction of ovulation with Pergonal and hCG. Radioligand-receptor assay of unextracted samples was subject to non-specific interference by plasma proteins, causing an apparent elevation of gonadotropin levels during the first few days after fertilization. By contrast, the gonadotropin values measured by a highly sensitive LH/hCG bioassay were consistent with those obtained with a sensitive and specific radioimmunoassay for hCG, and showed that the first significant rise in plasma hCG occurred 9 to 13 days after ovulation. These results indicate that hCG does not appear in the maternal circulation until after the initiation of implantation of the blastocyst.

PIP: A detailed study of the changes in plasma human chorionic gonadotropin (HCG) levels during early pregnancy was performed. Plasma HCG values, as determined by radioligand-receptor assay, were compared with those of radioimmunoassay and with a sensitive bioassay capable of measuring plasma levels of luteinizing hormone and HCG. Subjects were 4 women with secondary amenorrhea of hypothalamic origin. They were treated with human menopausal gonadotropin (Pergonal) followed by 10,000 IU of HCG to induce ovulation. Blood samples were collected at the time of HCG injection and at intervals of 1-2 days thereafter. Details of techniques used are given. Plasma proteins caused a nonspecific interference 1st significant rise in plasma HCG occurs 9-12 days after ovulation. Results indicate that HCG does not appear in the maternal circulation until after the implantation of the blastocyst.

Delayed pituitary hormone response to LRF and TRF in patients with anorexia nervosa and with secondary amenorrhea associated with simple weight loss.

The qualitative and quantitative responses of LRF-induced LH and FSH release and TRF-induced TSH and Prolactin (PRL) release were evaluated in 21 patients with anorexia nervosa, 19 patients with secondary amenorrhea associated with simple weight loss (SWL) who did not fulfill the psychologic criteria for anorexia nervosa, and 7 normal women in the early follicular phase of the menstrual cycle. Basal plasma LH and FSH were significantly lower in the anorexia nervosa group compared to the SWL group and normals (P less than 0.05). The LRF-induced integrated LH responses, however, were the same in the 3 groups and the integrated FSH responses were greater in the underweight groups when compared to normal. The time of the peak LH response (mean+/-SE) was signifantly delayed (P less than 0.01) in both the anorexia nervosa (49 +/- 6.1 min) and SWL (28 +/- 2.5 min) groups when compared to normal (17 +/- 2.3 min). The time of the FSH response was significantly delayed (P less than 0.05) in anorexia nervosa (95 +/- 9.6 min) when compared to normals (35 +/0 7.9 min) and SWL patients (62 +/- 11.7 min). Normal basal TSH and PRL and normal peak TSH and PRL responses to TRF were found in anorexia nervosa. The time of the TSH and PRL peak (56+/-8.9 and 36+/-3.6 min,, respectively) in anorexia nervosa was significantly later than normal (26 +/- 1.7 and 36 +/- 3.6 min respectively) (P less than 0.01). It is concluded that despite normal quantitative response to releasing hormones, there are abnormally delayed responses in both anorexia nervosa and SWL patients. The SWL responses were intermediate between those of the anorexia nervosa group and normals. The constellation of normal quantitative but abnormal kinetic LRF and TRF responses supports the hypothesis that the endocrine changes seen in anorexia nervosa are consistent with hypothalamic dysfunction.

Characterization of a small molecular size urinary immunoreactive human chorionic gonadotropin (hCG)-like substance produced by normal placenta and by hCG-secreting neoplasms.

Urine obtained from normal pregnant women as well as from patients with hCG-secreting tumors frequently contains native hCG and free hCG subunits when separated on Sephadex G-100. In addition, a small amount of an immunoreactive, hCG-like, low molecular weight substance is usually observed in those chromatograms and represents less than 1% of the total immunoreactive hCG present. Two patients with widely metastatic hCG-secreting tumors excreted disproportionately large quantities of that low molecular weight substance, and that observation raised the possibility that this substance was a secretory and not a degradative product of the hCG molecule. The small immunoreactive hCG-like substance was subsequently characterized immunologically, biologically, and physically. The hCG fragment displayed a biphasic dose-response line in a homologous hCG RIA. The slope of the upper portion of the dose-response line was equal to that for native hCG, but the slope of the lower component of the dose-response line was significantly different from that for hCG. The immunoreactive hCG substance cross-reacted with hCG beta but not with either hCG alpha or hCG beta carboxyl-terminus. The small molecular size immunoreactive hCG-like substance bound to Concanavalin A-Sepharose 4B and eluted with 0.2 M alpha-D-methyl glucopyranoside, contained no significant intrinsic biological activity when tested in the in vitro Leydig cell bioassay and also failed to compete with labeled hCG for specific ovarian LH/hCG receptors. Consequently, that small urinary immunoreactive hCG substance behaved neither as a hCG agonist or antagonist. It exhibited a plasma half-life of 4.5 min when the appropriate Sephadex G-100 fractions were injected into immature female rats. The small molecular size immunoreactive hCG-like substance may be a secretory or breakdown product of hCG-secreting cells.

Neuroendocrine dysfunction in temporal lobe epilepsy.

Since medial temporal lobe structures are involved in the modulation of endocrine function and temporal lobe epileptics commonly show personality changes that resemble endocrine disorders, the existence of neuroendocrine dysfunction in temporal lobe epileptics was investigated by comparing the response of serum luteinizing hormone levels with intravenous luteinizing hormone-releasing hormone infusion in patients and normal controls. Five of seven consecutive patients had response curves that fell almost entirely outside of the normal control range, and all seven had either baseline or peak values that were outside of the normal range. These findings suggest that hypothalamic-pituitary control of gonadotropin secretion may be altered among patients with temporal lobe epilepsy.

Reproductive endocrine disorders in men with partial seizures of temporal lobe origin.

Twenty consecutive men with partial seizures of temporal lobe origin were evaluated for sexual or reproductive dysfunction. Eleven (55%) had diminished sexual interest or reduced potency. Nine of them had reproductive endocrine disorders, with features of hypogonadotropic hypogonadism in five, hyperprolactinemia in two, and hypergonadotropic hypogonadism in two. Among these nine were cases in which the reproductive endocrine abnormalities could not readily be attributed to antiseizure medication use. Other possible interpretations are as follows: epileptic discharges in medial temporal lobe structures may disrupt hypothalamic regulation of pituitary secretion, hypogonadism may promote the development of epileptic discharges, and temporal lobe epilepsy and associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of both the brain and the reproductive system.

Reproductive endocrine disorders in women with partial seizures of temporal lobe origin.

Of 50 consecutive women with partial seizures of temporal lobe origin (temporal lobe epilepsy [TLE]) evaluated for reproductive dysfunction, 28 had menstrual problems. Of those, 19 had reproductive endocrine disorders. Polycystic ovarian syndrome and hypogonadotropic hypogonadism occurred significantly more often in women with TLE than in the general female population. Polycystic ovarian syndrome was associated with predominantly left-sided lateralization of interictal epileptic discharges; hypogonadotropic hypogonadism was more commonly found with right-sided discharges. Hyposexuality occurred more often in women with predominantly right-sided interictal epileptic discharges and was associated with low serum luteinizing hormone levels. There are several possible interpretations: epileptic discharges in medial temporal limbic structures may disrupt hypothalamic regulation of pituitary gonadotropin secretion; anovulatory cycles of reproductive endocrine disorders may promote the development of epileptic discharges; and TLE and some associated reproductive endocrine disorders may represent the parallel effects of prenatal factors common to the development of the brain and the reproductive system.

Rat ovarian subcellular compartmentalization of luteinizing hormone.

To determine if human luteinizing hormone (hLH) follows the same subcellular route in the pseudo-pregnant rat ovary as human chorionic gonadotropin (hCG), the distribution of immunoreactive and bioactive hLH within cytosol, lysosomes, and a combined plasma membrane/prelysosomal vesicle fraction was examined. Immunoreactive levels were determined using a specific radioimmunoassay and bioactive levels were determined in an in vitro Leydig cell bioassay. Low cytosolic hLH levels were apparent the first few hours after hLH administration and may reflect at least some contamination by serum and interstitial fluid. Plasma membrane/prelysosomal vesicles attained the highest hLH concentration 1 h after hLH injection, after which hLH levels declined rapidly until barely detectable levels were observed at 18 h. The hormone in this fraction was receptor bound and exhibited the highest bioactivity of the three fractions examined. Lysosomal hLH concentrations were highest at 12 after hLH injection and were maintained at high levels through 18 h. Substantial amounts of lysosomal hLH appeared to be receptor bound but this hormone was not bioactive. In situ degradation of the oligosaccharides may have occurred while lysosomal hLH was receptor bound. Lysosomal degradation is the major pathway for hLH inactivation as has been described for hCG. However, hLH may be degraded within lysosomes more quickly than hCG. The differential subcellular distribution of immunoreactive and bioactive hLH provides strong support for hLH internalization and degradation within ovarian luteal cells.

Shortened luteal phase after ovulation induction with human menopausal gonadotropin and human chorionic gonadotropin.

Serum hormonal profiles were characterized in 126 treatment cycles from 24 anovulatory women who underwent ovulation induction therapy with sequential human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Of the 98 presumptively ovulatory treatment cycles, 18 had luteal phases lasting 11 days or less. Sixteen of these 18 cycles had one or more of the following features: serum hCG concentrations of less than 75 mIU/ml 24 hours after hCG administration or peak preovulatory estradiol (E2) levels either less than 200 pg/ml or greater than 2000 pg/ml. Midluteal serum progesterone levels were less than 10 ng/ml in seven of the shortened cycles. Only one of these features (E2 greater than 2000 pg/ml) was present in any cycle (n = 2) resulting in pregnancy. Our observations suggest that serum E2 and hCG levels will reflect the apparent adequacy of luteal function during hMG/hCG treatment cycles.

Human chorionic gonadotropin as a tumor marker.

Ectopic production and secretion of hormones by a wide variety of tumors has been known for decades. Initially, ectopic hormone secretion was recognized by signs and symptoms of excess circulating biologically active hormone. With development of more sophisticated assay techniques, biologically inactive fragments and "big" forms of authentic hormones have been identified in these syndromes. Recently, a specific hCG assay has been developed for selectively measuring hCG in plasma samples containing both hLH and hCG. Studies reported to date suggest that hCG may be a good tumor marker. Using that assay system, several hundred sera obtained from patients with a wide variety of tumors were screened. Patients with tumors of the stomach, liver, ovary and testis were found to have the highest incidence of ectopic hCG secretion.