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Biomedical subjects

J L Vaitukaitis

Publications and source records attributed to J L Vaitukaitis.

At least 19 recordsLinked to original sources

Exercise-induced menstrual dysfunction.

Menstrual cycle changes associated with vigorous exercise can range widely. They may be only subtle abnormalities, ranging from delayed onset of spontaneous menses or anovulatory cycles to loss of spontaneous menses. They may be more serious, however. Significant adverse bone mineral changes, resulting in clinically significant osteoporosis and fractures, may occur concomitantly with exercise-induced menstrual dysfunction.

Amenorrhea↗

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.

Amino Acid Sequence↗

Divergent metabolism of human chorionic gonadotropin subunits within rat ovarian lysosomes.

Pseudopregnant rats were injected with either native human chorionic gonadotropin or with (125I)-human chorionic gonadotropin and their ovarian homogenates fractionated on Percoll density gradients. The levels of alpha and beta subunits within subcellular fractions were measured using radioimmunoassays specific for each subunit. Radioactivity measurements of fractions obtained from rats injected with (125I)-human chorionic gonadotropin were used as a separate index of alpha subunit distribution. The alpha subunit was primarily restricted to a combined plasma membrane/prelysosomal vesicle fraction. Immunoreactive beta subunit was present at high concentrations within both this plasma membrane/prelysosomal vesicle fraction and within lysosomes. The striking difference in alpha and beta subcellular distribution may arise from differential sensitivities to lysosomal enzymes.

Animals↗

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.

Adult↗

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.

Adult↗

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.

Animals↗

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.

Animals↗

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.

Animals↗