Striated palmoplantar keratoderma of Brunauer-Fohs-Siemens.

A 67-year-old African American man presented with callosities of his hands (which he had since adolescence) that were exacerbated by manual labor. His father suffered severe callosities of his feet, but no other family member was afflicted. Physical examination revealed symmetrically distributed linear hyperkeratotic plaques on the palms extending onto the full length of the volar aspect of his digits (Fig. 1). There was no personal or family history of hair, nail, or dental abnormalities. Histologic evaluation showed marked acanthosis, hypergranulosis, and hyperkeratosis of the lesions (Fig. 2). There was no evidence of epidermolytic hyperkeratosis.

Altered regulation of pituitary luteinizing hormone secretion by GnRH and inhibin in the aged persistent-estrous female rat.

The physiologic regulation of pituitary LH secretion is under the direct control of hypothalamic GnRH as well as feedback control via ovarian steroid and peptide hormones. Changes within the hypothalamic-pituitary-ovarian axis during reproductive aging lead to the gradual attenuation and the eventual loss of cyclic LH release that is seen in the old persistent-estrous rat. In the following studies, we determined whether changes in the pituitary response to regulation by hypothalamic GnRH and/or ovarian inhibin could be involved in age-related deficits in LH release by examining the direct effect(s) of GnRH and inhibin on LH release in old persistent-estrous (PE) and young female rats using an in vitro pituitary cell culture system. Both pituitary LH content and LH release were significantly lower in PE pituitary cells compared to young pituitary cells. GnRH (10 ng/ml) significantly increased LH release above basal levels in young and PE pituitaries. However, the magnitude of LH release was significantly lower in PE pituitaries compared to young pituitaries. Treatment with recombinant inhibin (0.1, 1, or 5 ng/ml) did not significantly affect basal or GnRH-stimulated LH release from young rat pituitaries under our culture conditions. In contrast, there were significant decreases in the levels of both basal LH and GnRH-stimulated LH release from PE pituitaries after treatment with 1 or 5 ng/ml human recombinant inhibin, as well as with inhibin plus 10 ng/ml GnRH, respectively. These results suggest that there are significant changes in the pituitary response to GnRH and ovarian inhibin regulation that may lead to significant alterations in LH secretion during aging.

Alterations in plasma and ovarian immunoreactive inhibin during reproductive aging in the female rat.

Previously, we showed that ovarian inhibin α- and ß;(A)-subunit mRNAs are elevated in middle-aged and old persistent-estrous (PE) female rats. To determine whether higher inhibin subunit mRNA expressions result in increased circulating inhibins during reproductive aging, plasma immunoreactive inhibin α (ir-inh α) and gonadotropins were measured in young, middle-aged and PE rats. Plasma LH profiles were distinctly divergent in the middle-aged rats with some showing LH surges indistinguishable from young rats and others showing significantly attenuated LH surges. Plasma ir-inh α in middle-aged rats with LH surges were similar to those of young rats. However, animals with attenuated LH surges had higher peak ir-inh α levels than young and middle-aged animals with LH surges. Immunohistochemistry revealed increased levels of ovarian inhibin α staining in those animals with attenuated LH surges. Overall, the highest plasma and ovarian inhibin α were found in PE rats which lack LH surges. However, significant decreases of plasma and ovarian inhibin α were seen after reinstatement of estrous cyclicity with progesterone implant treatment. Thus, increases in both plasma and ovarian inhibin α appear to be closely associated with attenuation or loss of the preovulatory gonadotropin surge that occurs during aging.

Expression of activin receptor II and IIB mRNA isoforms in mouse reproductive organs and oocytes.

Activins, the dimeric polypeptides of inhibin beta-subunits, exhibit paracrine effects on cell proliferation, differentiation, and various other cell functions. The complex biological response to activin appears to involve multiple receptors. In the present study, we examined the isoform mRNA expression of both activin receptor type II (ActR-II) and type IIB (ActR-IIB) genes in mouse reproductive organs, cumulus-oocyte complexes (COCs), and ovulated oocytes. Northern blot analyses of female and male reproductive organs with single-stranded ActR-II cDNA probes revealed that mouse ovaries expressed high levels of the 6.0 kilobase (kb) mRNA, whereas the 3.0 kb transcript was the major mRNA species found in the testis. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that both COCs and oocytes contained ActR-II mRNA. To examine the expression of ActR-IIB gene, primer selection was made outside the two alternative splicing sites in order to amplify the cDNAs of all four distinct receptor isoforms. The results of RT-PCR demonstrated that isoforms IIB2 and IIB4 were the major mRNA species expressed in both female and male gonads and extragonal reproductive tissues. The ovary expressed all four mRNA isoforms, whereas the testes expressed only three isoforms. whereas the testes expressed only three isoforms. Furthermore, COCs and oocytes contained only the ActR-IIB2 isoform. The differential expression of both activin receptor mRNA isoforms in the reproductive organs suggests that distinct alternative splicing mechanisms are involved in activin receptor gene expression in male and female gonads, and that each of the activin receptors may have its own biological function in reproduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced ovarian inhibin subunit gene expression in aging rats is due to chronic anovulation.

The persistent-estrous (PE) state in aging rats, characterized by a lack of ovulation and absence of estrous cycles, is associated with enhanced inhibin alpha and beta A subunit mRNA expression in the ovaries. It has been shown that the PE state can be interrupted by successive treatments with a progesterone implant (P-implant) and that estrous cycles can be transiently restored after implant removal. The present study examined whether restoration of estrous cycles in PE rats could reverse the altered ovarian inhibin alpha and beta A subunit gene expression. PE rats were treated with subcutaneous P-implants for 6 wk. After implant removal, the return of estrous cyclicity was confirmed by characteristic cyclic changes in vaginal cytology. Ovaries collected from the P-implant-treated animals at 1100 h on diestrus Day 2 or proestrus showed significantly decreased levels of both inhibin alpha and beta A subunit mRNAs compared to those of PE controls and young cyclic females. In situ hybridization revealed that the decreased inhibin alpha subunit mRNA after P-implants was due to decreased gene expression in the granulosa cells of large preovulatory follicles and to a compete absence of gene expression in large, cystic follicles devoid of granulosa cells and oocytes. In addition, inhibin alpha subunit mRNA was expressed in the newly developed follicles after implant removal. The beta A subunit mRNA was detected only in maturing follicles, not in newly developing follicles or in the large cystic follicles. The patterns of ovarian inhibin alpha and beta A subunit gene expression mimicked those of cyclic animals. These data indicate that loss of estrous cycles in aging rats results in an overexpression of inhibin alpha and beta A mRNAs in large and anovulatory follicles and that reinstatement of ovarian cycles in aged rats restores inhibin gene expression to normal levels.

Relationship of sperm antibodies in women and men to human in vitro fertilization, cleavage, and pregnancy rate.

PROBLEM: The presence of anti-sperm antibodies (ASA) in female serum has been correlated with decreased fertilization in the in vitro fertilization (IVF) program; however, the impact of each type of ASA (IgG, IgA, IgM) is not known. METHOD: To clarify the role of each ASA subtype, the immunobead binding technique was used to identify IgG, IgA, and IgM ASA in the female sera and on the spermatozoa from 137 couples undergoing the IVF program. RESULTS: Couples with ASA on spermatozoa had a lower fertilization rate and lower number of transferred embryos: and IgG was the major immunoglobin involved. Couples with ASA in female sera showed significant decreases in the rates of fertilization, cleavage, and number of transferred embryos only when IgM was detected, but not IgG or IgA. However, the presence of IgA ASA in female sera was only associated with a decrease in pregnancy rate, although the number of transferred embryos was not reduced. CONCLUSION: These findings suggest that ASA can influence the results of IVF and that the specific effect is dependent upon the subtypes of ASA.

Alterations in the postovariectomy increases in gonadotropin secretion in middle-aged persistent-estrous rats: correlation with pituitary gonadotropin subunit gene expression.

This study compared the changes in pituitary and serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at various times following ovariectomy (OVX) between young cyclic and middle-aged persistent-estrous (PE) rats and related these to the relative gene expression of the pituitary gonadotropin subunits. In intact animals, both pituitary and serum levels of LH were similar between these two age groups, while the LH beta mRNA expression was significantly (p < 0.05) greater in young rats. Following OVX in young rats, the serum LH levels markedly increased (p < 0.05) beginning on day 7 and reaching a maximum fourfold increase by day 9. In contrast, the post-OVX increases in serum LH in middle-aged females were significantly delayed. OVX significantly (p < 0.05) increased pituitary LH contents of young rats by day 5, but had no effect on LH contents in middle-aged females until day 30 post-OVX. These changes were associated with increases in LH beta mRNA expression in both young and middle-aged females, but the levels were significantly (p < 0.05) lower in middle-aged females. Both pituitary and serum levels of FSH were significantly (p < 0.05) higher in middle-aged PE than in young rats prior to OVX, while the FSH beta mRNA expression was similar in both age groups. Following OVX in young rats, serum FSH levels rapidly increased (p < 0.05) on day 3 and attained tenfold higher values by day 30.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibin subunit gene expression and distribution in the ovaries of immature, young adult, middle-aged, and old female rats.

In young adult female rats, the patterns of inhibin subunit mRNA expression during the estrous cycle are regulated by cyclic changes in gonadotropin secretion and follicular development. Since there are distinct alterations in profiles of both hormone secretion and folliculogenesis during the reproductive lifespan of the female rat, we have characterized the gene expression and distribution of inhibin subunit mRNAs in immature (22 days), young adult cyclic (3-4 months), middle-aged cyclic (9-10 months), and old (12-13 months) persistent estrous (PE) rat ovaries. Northern blot analyses revealed that in contrast to young adult cyclic rats, inhibin alpha- and beta A-subunit mRNA levels in the ovaries of middle-aged cyclic rats remained substantially elevated after the proestrous gonadotropin surges and ovulation. Likewise, acyclic immature and old PE rats showed high levels of inhibin alpha- and beta A-subunit transcripts in their ovaries. In situ hybridization analyses demonstrated that inhibin alpha- and beta A mRNAs were abundantly expressed in maturing follicles of both young and middle-aged cyclic females, while high levels of alpha-subunit transcripts were only detected in the ovarian stroma of middle-aged animals. The ovaries of old PE rats had numerous large cystic follicles (with variable layers of granulosa cells) and few degenerating cyst-like structures (completely devoid of granulosa cells). Inhibin subunit transcripts were expressed abundantly in both the granulosa (alpha and beta A-subunits) and theca interna (alpha-subunit only) layers of large follicles, but were absent from degenerating cysts devoid of granulosa cells. The ovarian stroma of PE rats also expressed very high levels of inhibin-alpha, but not beta A mRNA. The ovaries of immature rats contained large numbers of uniformly developing secondary follicles. High levels of inhibin-alpha mRNA were expressed homogeneously in the granulosa layer of all growing follicles, whereas inhibin beta A mRNAs were only detected in selectively larger follicles with multiple layers of granulosa cells. Hormone RIAs of serum samples from these same groups of animals showed that basal levels of serum FSH were substantially higher in immature, middle-aged cyclic, and old PE rats than in young adult rats. These results demonstrate that enhanced ovarian inhibin subunit gene expression in the female rat is associated with increased serum FSH levels regardless of chronological age. On the other hand, aging appears to selectively enhance inhibin alpha, but not beta A, gene expression in the ovarian stroma, such that it may gradually become a major secondary site of alpha-subunit mRNA production in addition to the follicular compartments.

Differential distribution of glycoconjugates in human reproductive tract.

OBJECTIVES: To study the distribution of glycoconjugates in the epithelia of various regions of the human female reproductive tract and to examine whether lectins can be used as specific probes to define cell populations in the human female reproductive tract. DESIGN: Nineteen fluorescein isothiocyanate (FITC)-labeled lectins, which recognize different oligosaccharide structures, were applied to frozen sections of human fallopian tubes (distal and proximal segments) and endometrium. The differential binding patterns of the lectins to the epithelia were evaluated under fluorescent microscopy. RESULTS: Four of 19 FITC-labeled lectins tested demonstrated distinct binding patterns along the reproductive tract. Arachis hypogaea (PNA) and Ricincus communis II selectively reacted with epithelial cells of endometrium and distal, but not proximal tube. In addition, PNA distinguished ciliated from secretory cells of the distal tube. Maclura pomifera binding followed a gradient of decreasing intensity from distal to proximal tube and was negative in the endometrium. Dolichos biflorus reacted exclusively with proximal tubal epithelium. CONCLUSIONS: Analysis of the FITC-lectin binding pattern and the sugar specificities indicate that the distribution of galactosyl residues varies among different regions of the reproductive tract, whereas glucosyl, mannosyl and fucosyl residues are more evenly distributed. The differential expression of glycoconjugates may be involved in the distinct biological function of each region in female reproductive tract.