Follicular Cycle Research Articles

Growth hormone deficiency as the only identifiable cause for primary amenorrhea

Background: There is much evidence that growth hormone plays an important role in the development and function of the reproductive system of both males and females. Growth hormone exerts its effects on the ovarian follicular cycle directly or by local production of insulin-like growth factor 1 (IGF-1). It is known that growth hormone deficiency during childhood may delay pubertal development, but there is limited data about primary amenorrhea in GH-deficient girls with sufficient stimulated gonadotropin levels.Methods: Case series.Results: In the evaluation of primary amenorrhea and delayed puberty, 3 cases of adolescent females aged 17–19 years were identified as isolated GH-deficiency. Among the 3 patients, 2 had history of intracranial surgery due to hydrocephalus (shunt operation) or prolactin-secreting pituitary macro-adenoma (transphenoidal surgery, one year before). 17-year-old patient with shunted hydrocephalus and 19-year-old patient with primary amenorrhea showed short statue (< 5%) and delayed bone maturation. The patient undertaken transphenoidal surgery for prolactinoma showed normal height and bone maturation. There was no familial history of delayed puberty. On physical examination, 3 patients showed variable degree of breast development from Tanner stage II to IV without sex-steroid replacement. In sella MRI, small pituitary gland were identified in 2 patients with short statue and delayed bone maturation. All of the 3 patients underwent combined pituitary function test. After insulin-induced hypoglycemia, peak growth hormone levels of the 3 patients were 0.08, 1.4 and 1.4 ng/ml and were compatible with growth hormone deficiency. Peak LH after intravenous gonadrelin (FACTREL) were 19.0 to 56.1 mIU/ml and LH % responses were 217 to 1100% and were hence defined as not being gonadotropin deficiency. Other anterior pituitary functions were normal in all of the 3 patients.Conclusions: We found isolated growth hormone deficiency as the only identifiable cause for primary amenorrhea in three patients with sufficient gonadotropins secretion. These findings suggest a complementary role of GH to gonadotropins in the occurrence of menarche.

Reproductive hormone profiles in mares during the autumn transition as determined by collection of jugular blood at 6 h intervals throughout ovulatory and anovulatory cycles

The aim was to define precisely the FSH secretion pattern in mares during the two ovulatory cycles before, and for 24 days after, the last ovulation of the season and to compare this with the profiles of other reproductive hormones and follicular growth to identify changes which may lead to the termination of follicular cycles. Jugular blood was collected every 6 h from ten light horse mares for 6 weeks in autumn. Samples were assayed for FSH, LH, prolactin, inhibin, oestrone conjugates and progesterone. Luteolysis occurred earlier and periovulatory oestrone, but not inhibin, concentrations were significantly lower in the last than in the second to last cycles. In ovulatory and anovulatory cycles, daily mean FSH concentrations were low at the expected time of ovulation and high between days 9 and 11 (day 0 = ovulation), which were usually after luteolysis. However, the periovulatory FSH nadir was prolonged in the last compared with the second to last cycles, and the difference between peak and trough values was not significant in anovulatory cycles. Between day 5 and day 8, the FSH interpulse interval was approximately 2 days, and did not vary in successive cycles. The LH profile also showed progressive changes as mares entered acyclicity; the surge terminated sooner in the last than in the second to last cycles, and failed to occur when expected in acyclicity. Sporadic prolactin pulses occurred at luteolysis in a similar proportion of ovulatory and anovulatory cycles. These results indicate that inadequate gonadotrophin stimulation in early dioestrus may be a critical event leading to suboptimal follicular and luteal development, and eventually acyclicity. Moreover, the time relationships amongst changes in pituitary and ovarian hormones and follicular growth become increasingly disrupted during the autumn transition, which may contribute to the cessation of cyclicity.

Reproductive hormone profiles in mares during the autumn transition as determined by collection of jugular blood at 6 h intervals throughout ovulatory and anovulatory cycles

The aim was to define precisely the FSH secretion pattern in mares during the two ovulatory cycles before, and for 24 days after, the last ovulation of the season and to compare this with the profiles of other reproductive hormones and follicular growth to identify changes which may lead to the termination of follicular cycles. Jugular blood was collected every 6 h from ten light horse mares for 6 weeks in autumn. Samples were assayed for FSH, LH, prolactin, inhibin, oestrone conjugates and progesterone. Luteolysis occurred earlier and periovulatory oestrone, but not inhibin, concentrations were significantly lower in the last than in the second to last cycles. In ovulatory and anovulatory cycles, daily mean FSH concentrations were low at the expected time of ovulation and high between days 9 and 11 (day 0 = ovulation), which were usually after luteolysis. However, the periovulatory FSH nadir was prolonged in the last compared with the second to last cycles, and the difference between peak and trough values was not significant in anovulatory cycles. Between day 5 and day 8, the FSH interpulse interval was approximately 2 days, and did not vary in successive cycles. The LH profile also showed progressive changes as mares entered acyclicity; the surge terminated sooner in the last than in the second to last cycles, and failed to occur when expected in acyclicity. Sporadic prolactin pulses occurred at luteolysis in a similar proportion of ovulatory and anovulatory cycles. These results indicate that inadequate gonadotrophin stimulation in early dioestrus may be a critical event leading to suboptimal follicular and luteal development, and eventually acyclicity. Moreover, the time relationships amongst changes in pituitary and ovarian hormones and follicular growth become increasingly disrupted during the autumn transition, which may contribute to the cessation of cyclicity.

Reproductive endocrinology of female elasmobranchs: Lessons from the little skate (Raja erinacea) and spiny dogfish (Squalus acanthias)

Conventional classification of reproductive modes in female elasmobranchs fails to account for the diversity in ovarian dynamics that operate during oviparous and viviparous cycles. Delineating this diversity is crucial for understanding the endocrine regulation of the manifold physiological mechanisms utilized to retain and protect eggs and developing embryos, to fuel embryogenesis, and to manage the intrauterine milieu. Oocyte development and follicular steroidogenesis overlap with egg retention and pregnancy in some species, whereas in others the follicular phase of the cycle is temporally separated from the gravid period. A luteal phase predominates the post-ovulatory period in viviparous species. In oviparous species, the luteal phase overlaps with the follicular cycle. This heterogeneity in ovulatory cycles suggests that the endocrine system evolved a transmutable system for regulating steroidogenesis and the control of the reproductive events. The reproductive biology and endocrinology of the oviparous little skate and lecithotrophic viviparous spiny dogfish are reviewed in order to derive a working hypothesis that explains the complex nature of endocrine patterns observed in species utilizing disparate reproductive modes. An understanding of the adaptations in ovarian dynamics to particular ovulatory cycles is key to developing theories about the evolution of reproductive strategies in female elasmobranchs. J. Exp. Zool. 284:557–574, 1999. © 1999 Wiley-Liss, Inc.

Effects of Testosterone on Sexual Behavior and Morphology in Adult Female Leopard Geckos, Eublepharis macularius

The leopard gecko, Eublepharis macularius, is a species in which testosterone (T) is the primary circulating sex hormone in adults of both sexes. There are, however, sex differences in T physiology. Whereas males have prolonged periods with high T levels, T levels cycle in accord with follicular development in females. Specifically, T concentration increases during vitellogenesis, drops after ovulation, and then remains at previtellogenic levels until eggs are laid and the next follicular cycle begins. To determine the function of T in females, we manipulated both the level and the duration of T elevation using Silastic implants in intact, adult female leopard geckos. Females had low (∼1 ng/ml), medium (∼100 ng/ml), or high (∼200 ng/ml) T levels for either a short (8 days) or a long (35 days) duration. Behavior tests with males were conducted on days 1–5 in the short-duration group or on days 29–33 in the long-duration group. For both short- and long-duration groups, T treatment decreased attractivity in females with medium and high T levels compared to females with low T levels. In contrast, females with a medium T level were more receptive than females with a low T level in the short-duration group. Females in the long-duration group were unreceptive regardless of T level. Females treated for a long duration also displayed more aggression toward and evoked more aggression from males than short duration females. Short-duration T treatment had no masculinizing effect on female morphology, whereas medium and high T levels for a long duration induced development of hemipenes. Overall, these results suggest that T can both increase and decrease sexual behaviors in the female leopard gecko.

Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell.

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.

Morphological and morphometrical study on the dorsal skin of Wistar and WBN/ILA-Ht rats in their developing stage. Evaluation of the proliferation and apoptotic processes.

The detailed histology of the dorsal skin of Wistar-derived hypotrichotic WBN/ILA-Ht rats (HtRs) was examined in their developing stage (at 3 and 7 weeks of age) using Wistar rats (WRs) as controls. As a result, except for the existence of time-lag in the hair follicular cycle and some quantitative differences, there were no essential qualitative differences between the two strains. The follicular epithelial cell number and the amounts of tonofilaments and trichohyalin granules were less in HtRs than in WRs in the same phase of hair follicular cycle. In addition, the diameter of hair shaft was significantly larger in WRs than in HtRs at 7 weeks of age. The number of proliferating cell nuclear antigen (PCNA)-positive epidermal basal cells decreased in HtRs and increased in WRs from 3 to 7 weeks of age, respectively. Apoptosis was sparsely observed in the sebaceous gland epithelial cells, keratinizing portion of hair cuticules and inner root sheath in both strains, but the frequency of apoptosis in the hair follicle was somewhat higher in 7-week-old HtRs. HtRs are considered to be useful experimental animals for dermatotoxicological studies.

Clinical observation on effect of yangjing decoction in promoting follicular growth

To investigate the effect of Yangjing Decoction (YJD, a Chinese prescription of replenishing Kidney essence) in promoting follicular growth and its influence on blood supply of ovary and uterus. Twenty-two cases with secondary amenorrhea and 4 cases of infertility with infrequent menstruation caused by follicle maldevelopment were treated with YJD. The blood supply of ovary and uterus in 7 cases was measured by colour Doppler before and after treatment. Of the 116 therapeutic cycles in 26 cases, there were 69 menstrual cycles (59.48%), 37 follicular maturation cycles (31.90%), 21 ovulation cycles (18.10%), and the follicular maturation rate was 84.62%, The disturbance in blood supply of ovary and uterus was improved remarkably along with follicular development by YJD in 7 cases. YJD could improve follicular development and blood supply of ovary and uterus.

Folliculo‐sebaceous cystic hamartoma is a trichofolliculoma at its very late stage

Folliculo-sebaceous cystic hamartoma (FCH) was described as an entity recently and was defined as an adnexal hamartoma, showing above all an infundibular cystic structure linked to many sebaceous lobules. Differentiation toward the inferior segment of the hair follicle also occurs, although to a markedly lesser degree. Signs of regression and rest corresponding to the normal follicular cycle are often apparent in these follicular proliferations. Therefore so-called FCH has much in common with the newly described late stage of trichofolliculoma, which also exhibits an infundibular cyst and sebaceous and follicular differentiation with various signs of catagen and telogen. Comparing our 8 cases of FCH and 31 cases of trichofolliculoma, we came to the conclusion that FCH is the very late stage of trichofolliculoma. This stage could be characterized by a nearly complete regression of the transient follicular epithelium, whereas concurrent growth and maturation of sebaceous elements appear.

The trichofolliculoma undergoes changes corresponding to the regressing normal hair follicle in its cycle.

The trichofolliculoma is a follicularly differentiated hamartoma, usually described as showing many vellus follicles, spreading from a central infundibular cyst. In spite of the well known regressive changes of normal hair follicles during catagen and telogen, the possibility of corresponding changes in the trichofolliculoma has not yet been discussed in the literature. By examining a total of 31 cases of trichofolliculoma it is demonstrated that this hamartoma undergoes an evolutionary process with great morphological changes, which can be attributed to the anagen, catagen, and telogen phase of the follicular cycle.

Oocyte sensitivity to serotonergic regulation during the follicular cycle of the teleost Fundulus heteroclitus.

In the teleost Fundulus heteroclitus, serotonin (5-HT) reversibly inhibits oocyte maturation induced in vitro by the maturation-inducing steroid (MIS) 17,20beta-dihydroxy-4-pregnen-3-one (17,20betaP). The 5-HT inhibition of 17,20betaP-induced meiotic maturation was examined in ovarian follicles at different developmental stages or isolated at different times during the follicular cycle. Steroid treatment of late vitellogenic and early maturing follicles (1.2- to 1.7-mm diameter) promoted oocyte maturation in a size-dependent manner, and this maturation was inhibited by 5-HT in follicles of < 1.6- to 1.7-mm diameter. Thus, the 5-HT inhibition progressively decreased as follicles developed the ability to mature in the absence of 17,20betaP. The effectiveness of 5-HT to increase follicular cAMP remained similar within the same developmental stages, indicating that the reduction of 5-HT inhibitory action was not related to the competence of 5-HT to activate inhibitory signals in the oocyte. During the follicular cycle, fully grown follicles (1.3- to 1.4-mm diameter) showed a decreased maturational competence in response to gonadotropin or MIS stimulation after the follicular recruitment into maturation and spawning occurred, which coincided with an increase of the effectiveness of 5-HT at inhibiting 17,20betaP-induced maturation. In further experiments, preincubation of follicles with hCG was found to reduce 5-HT inhibitory action, but when follicles were incubated with either hCG in the presence of a steroidogenesis inhibitor or estradiol-17beta (E2), the 5-HT inhibition was unaffected. These findings suggest that 5-HT inhibition of the MIS-induced meiotic maturation is not under direct gonadotropin or E2 regulation but that it might be regulated in vivo by changes in the competence of the oocytes to undergo oocyte maturation after MIS stimulation.

Immunohistochemical investigation of the different developmental stages of trichofolliculoma with special reference to the Merkel cell

The morphologic features of trichofolliculoma are variable, reminiscent of the anagen, catagen, and telogen phases of a normal hair follicle in its cycle. We recently described an early, fully developed stage and late stages of trichofolliculoma. Using immunohistochemical examination, we sought to demonstrate hyperplasia of Merkel cells in all three stages of trichofolliculoma. We found this to be the most striking in small lesions of the late stage. The distribution of the Merkel cells in several stages of trichofolliculoma coincided with the known arrangement of normal follicular Merkel cells during the follicular cycle. However, antibodies against neurofilaments failed to detect innervated Merkel cells, in contrast to normal follicular Merkel cells. Antibodies against Ki67 did not reveal proliferative Merkel cells in any of the trichofolliculomas, but for unknown reasons, a distinct cytoplasmic staining of Merkel cell processes sometimes occurred. Nuclear Ki67 was strongly expressed in the nuclei of follicular keratinocytes of the fully developed trichofollicullomas, whereas those at a late stage showed a markedly decreased staining pattern. Our finding of Merkel cells in all trichofolliculomas underlines their classification as hamartomas with follicular differentiation. Hyperplasia of Merkel cells, even in trichofolliculomas at a late stage, as regressing lesions might implicate hitherto unknown regulatory functions of this neuroendocrine cell.

Pattern of Vitellogenesis and Follicle Maturational Competence during the Ovarian Follicular Cycle ofFundulus heteroclitus

The patterns of vitellogenesis and follicle maturational competence were examined across the semilunar spawning cycle ofFundulus heteroclitus.Daily egg collection showed spawning cyclicity in six experimental groups, with a mean period between spawnings of 14.9 ± 0.3 days, indicated by the nonlinear regression sine-curve matching analysis. Each cycle was then dated from Day −7 to Day 7, with Day 0 as the peak egg-collection day. Females from each group were sampled on selected days during two to three consecutive spawning cycles, and these days were each chronologically given a temporal relation to Day 0 to pool the data into a composite. The analysis of the size–frequency distribution of ovarian follicles ≥0.5-mm diameter across the composite revealed a constant recruitment of small follicles (0.5- to 0.7-mm diameter) into vitellogenesis, which was supported by the continuous presence of vitellogenin (Vtg) I mRNA in the liver of the females. The plasma levels of Vtg were also essentially constant across the cycle, except for a progressive decrease from Day −7 through Day 3 that could be related to a more active Vtg uptake by a dominant population of follicles up to 1.7 mm in diameter. A second and more selective recruitment of full-grown follicles (1.3- to 1.4-mm diameter) toward maturation was noted at Days −5, −4, which appeared associated with high plasma levels of estradiol-17β. However, the responsiveness of those follicles undergoing oocyte maturationin vitroafter gonadotropin and maturation-inducing steroid (MIS), 17,20β-dihydroxy-4-pregnen-3-one, stimulation dramatically declined from Days −1, 0, 1 to Days 4, 5, concomitantly with an increase of the population of the largest follicles (1.8- to 2.1-mm diameter) in the ovary. These findings extend previous observations on the process of follicular recruitment inF. heteroclitusand indicate that full-grown follicles may be recruited into maturation by a mechanism that modulates the oocyte sensitivity to the MIS.

Semilunar follicular cycle of an intertidal fish: the Fundulus model.

In their habitat, Fundulus heteroclitus (Cyprinodontidae) spawn against a variety of specific substrates that become available only at spring tides; they thus exhibit a semilunar reproductive cyclicity. In the laboratory at 28 +/- 0.6 degrees C and 14L:10D, this cyclicity is free-running and can be observed by means of daily egg collection and frequent ovarian sampling. Daily egg collection cycles gathered from three different spawning groups were pooled chronologically; the cycles were determined by nonlinear regression sine-curve matching and so were dated from Days -6 to +6, with Day 0 as the peak egg collection day. Ovaries were sampled on Days -6, -4, -2, -1, +1, +2, and +4. The pooled data indicated that early-maturing follicles (1.3- to 1.6-mm diameter) are recruited from a constant reserve of vitellogenic follicles (0.7- to 1.2-mm diameter) and become abundant early in the cycle but are depleted during Days -6 to +4 by the formation of late-maturing follicles and ovulated eggs. A midcycle peak of ovulated eggs in the ovary corresponds to the egg collection peak. This progression of follicles followed by spawning decreases the total count of the follicles (> or = 0.7-mm diameter) and eggs in the ovary by 52% (from 454 to 219 per 10 g of female weight). The semilunar follicular cycle in this Fundulus model thus includes 1) an early-cycle follicle recruitment, 2) an early- and midcycle follicle maturation, and 3) a midcycle egg ovulation and spawning. This follicular cycle also proceeds in fish deprived of a spawning substrate. A female in the wild would thus execute the follicular cycling in a timely sequence, in anticipation of each recurring spring tide, whether or not a natural substrate becomes available. We conclude that F. heteroclitus provides a useful nonmammalian model for the study of cyclic reproductive activity in the laboratory.

The ovarian follicular wave pattern and induction of ovulation in the mated and non-mated one-humped camel (Camelus dromedarius)

Ovarian follicular wave patterns were studied ultrasonographically in three groups of dromedary. Group 1 camels (n = 20) were teased daily with a vasectomized male but mating was prevented; group 2 camels (n = 8) ran freely with a vasectomized male camel for 10 h each day and group 3 camels (n = 8) were kept completely separate from any males. In a second experiment (n = 63), when the diameter of the dominant follicle reached 0.5-0.9 cm, 1.0-1.9 cm, 2.0-2.9 cm or > 3 cm, the camel was given one of three treatments to induce ovulation: (i) natural mating; (ii) 20 micrograms of the GnRH analogue, buserelin; or (iii) 3000 iu hCG. The ovaries were re-scanned regularly to monitor ovulation, and daily blood samples were assayed for progesterone and oestradiol concentrations. The follicular cycle was divisible into a growth phase (10.5 +/- 0.5 days), a mature phase (7.6 +/- 0.8 days) and a regression phase (11.9 +/- 0.8 days). The dominant follicle reached a mean +/- SEM maximum diameter of 2.0 +/- 0.1 cm (range 1.5-2.5 cm) in 34 cycles (52%) before it began to regress. In the other 32 cycles (48%), however, the dominant follicle continued to grow to 4.2 +/- 0.2 cm (range 4.0-6.0 cm) before regression commenced. Group 2 camels were mated when their follicles reached 1.3 +/- 0.1 cm in diameter and the mean interval between successive matings was 13.8 +/- 1.0 days. Mean +/- SEM serum concentrations of oestradiol reached peak values at 39.0 +/- 1.8 pg ml-1, when the dominant follicle measured 1.7 +/- 0.1 cm and, after ovulation, mean serum concentrations of progesterone reached peak values at 2.6 +/- 0.3 ng ml-1 on day 8, before decreasing to < 1 ng ml-1 by day 10 or 11. When the dominant follicle measured 0.5-0.9 cm in diameter, 70%, 60% and 60% of them ovulated in response to mating, or treatment with buserelin or hCG, respectively. These ovulation rates increased to 85% (mating), 81% (buserelin) and 67% (hCG) when the follicle measured 1-1.9 cm, but they decreased again to 12.5% (mating), 29% (buserelin) and 13% (hCG) when the diameter had increased to 2.0-2.9 cm at the time of treatment. No follicles measuring > 3.0 cm ovulated in response to any of the treatments. These results indicated that the optimum time to mate or attempt to induce ovulation in the female dromedary is when the growing follicle measures 0.9-1.9 cm in diameter.

The hair follicular cycle of the cryptothrix mouse and the characteristics of its abnormal hair

The hair follicular changes of the cryptothrix mutant mouse (crh mouse) were examined sequentially from birth to 365 days of age and the characteristics of the abnormal hair were observed. The homozygous crh mouse had no hair coat on the skin surface during the period of observation, but a small number of fuzzy soft hairs in the black pigmented skin of the anagen phase was seen. Cyclic folliculogenesis, however, was observed histologically in the dermis. The first anagen phase developed at 3 to 4 days of age and lasted until about 15 days of age. The hair follicles then entered the telogen phase, which lasted until about 18 to 32 days of age. Thereafter, the follicular cycles were repeated three times about every 20 days until 90 days of age. This pattern coincided well with the normal hair cyclic pattern reported for the mouse and rat. After 100 days of age, however, alternating anagen and telogen phases formed a striped pattern in the skin, with black bands. These black bands became progressively thinner and shifted anteriorly, showing a wavy pattern. The abnormal hair of the homozygous crh mouse showed separation of the hair medulla due to incomplete trichilemmal keratinization in the internal root sheath. The tips of the hair shafts were folded and collapsed under the epidermis and did not erupt on the skin surface. The hair follicles, however, did not differ from those of heterozygous crh mice. Because the homozygous crh mouse failed to form a complete hair shaft, cyclic folliculogenesis of the epidermis could be easily observed macroscopically without depilation. The homozygous crh mouse may prove useful in evaluating new drugs for hair follicular growth.

Regulated storage and subsequent transformation of spermatozoa in the fallopian tubes of an Australian marsupial, Sminthopsis crassicaudata.

The disposition of spermatozoa in the female tract of the dasyurid marsupial, Sminthopsis crassicaudata, was examined before and after ovulation, by transillumination using differential interference optics. At 6-30 h after mating in females with maturing follicles, spermatozoa were restricted to special storage crypts that define the isthmus of the Fallopian tube. These spermatozoa were mostly immotile and were spear shaped, except for 50-200 vanguard spermatozoa within anterior crypts that were T shaped due to a rotation of the head on the tail. After ovulation and arrival of eggs in the narrow upper ovarian segment of the tube, several hundred isthmic spermatozoa migrated to that region, dispersed singly or in small groups of variable motility with some festooned around eggs. Most clearly displayed a T configuration, and subsequently, those remaining in the isthmic crypts also adopted a T shape in situ. The motility of mature epididymal spermatozoa and of those flushed from the isthmus before and after ovulation was similar in vitro, and all were spear shaped except for some T-shaped isthmic spermatozoa recovered after ovulation. However, neither spear- nor T-shaped active isthmic spermatozoa ever adhered to the zona pellucida when incubated with eggs. We conclude that transport to and storage of spermatozoa in the isthmus of the Fallopian tube, and their later migration up to the fertilization site and coincident transformation to a T shape, all are closely regulated by the ovarian follicular cycle in Sminthopsis. Only on reaching the upper ovarian segment of the Fallopian tube do Sminthopsis spermatozoa appear to be able to bind to the egg, when the T shape brings the whole surface area of the acrosome into apposition with the zona pellucida. These observations are discussed with special reference to sperm capacitation, sperm penetration mechanisms, and the different idiosyncratic designs of the sperm head in marsupial and eutherian mammals, respectively.

Immunoreactivity of antibodies to epidermal growth factor, transforming growth factors alpha and beta, and epidermal growth factor receptor in the premenopausal ovary

This study provides a valuable insight into the localization of growth factors in paraffin sections of human ovarian tissue. Antibodies to epidermal growth factor (EGF), transforming growth factors alpha and beta (TGF alpha and beta) and epidermal growth factor receptor (EGFR) were applied to paraffin sections of 16 cases of formalin-fixed normal or benignly abnormal ovarian tissue. All growth factor antibodies reacted with theca, but not granulosa cells, whilst the antibody to EGFR reacted with both types of follicular cells and was weakly reactive in ovarian stroma. There were no discernible qualitative changes in reactivity during the follicular cycle. These immunohistochemical findings generally support previously published molecular and biochemical data from tissue culture. One exception is in the observation of immunoreactivity to EGF in theca and granulosa cells. This may be due to differences in sensitivity of the methods in use. The possibility of a cross-reaction of the anti-EGF antibody with TGF alpha is also discussed. This study provides evidence for both paracrine and autocrine roles for growth factors in folliculogenesis.

Suppression of Plasma Insulin-Like Growth Factor-1 Levels in Healthy, Nulliparous, Young Women Using Low Dose Oral Contraceptives

Insulin-like growth factor-1 (IGF-1) levels were analyzed in 43 healthy, nulliparous women aged 19-25 years. Blood samples were drawn in a standardized way in follicular and luteal phases, for present users during cycle days 5-10 and 18-23, respectively. In each women, absolute levels and a difference in p-IGF-1 levels between the two menstrual cycle phases (delta IGF-1) were related to oral contraceptive (OC) use, height, weight, age, gonadotropin and serum sexual hormone binding globulin (s-SHBG) levels. In the follicular phase and cycle days 5-10, absolute values of p-IGF-1 did not significantly differ between present, former and never users of OCs, in contrast to a significant difference (p = 0.0013) in the luteal phase and cycle days 18-23 between present users and never users, after adjustment for age. delta IGF-1 was significantly negatively correlated to present OC use, compared with nonusers (p = 0.0002). delta IGF-1 did not significantly differ between former and never users. While height and weight were not significantly related to delta IGF-1, there was a significant negative correlation between age and delta IGF-1 (p = 0.05). Also, s-SHBG and p-IGF-1 were significantly negatively related in the luteal phase and cycle days 18-23 after adjustment for age (p = 0.006), although this relationship disappeared after adjustment for present OC use.

Bulge-Activation Hypothesis

This essay is a critique of a revolutionary hypothesis, and of the language used to frame it, that offers a novel interpretation for the dynamics of the follicular cycle by distinguishing, distinctly, germinative cells in the bulge from matrical cells in the bulb. Curiously, this intriguing "bulge-activation hypothesis" elicited practically no response in the scientific literature, and our critique is designed to rectify that.