Normal Sexual Maturation Research Articles

Testosterone Therapy for Pubertal delay

Despite considerable variation in the age at which puberty normally begins, a male adolescent who has demonstrated neither testicular nor pubic hair growth by 14 years of age is considered to have delayed puberty. Although such delay may indicate hypopituitarism or isolated gonadotropin deficiency, most commonly it represents a normal variation, termed "constitutional delay in growth and maturation." Such patients eventually will enter puberty and achieve normal sexual maturation and adult height. However, during adolescence, such delays may be accompanied by impaired self-image and social isolation. Under these conditions, many pediatric endocrinologists advocate short-term use of anabolic steroids. Such therapy is aimed at accelerating height velocity during the ensuing year, accompanied by the development of age-appropriate secondary sexual characteristics.

Effect of Age at the Start of Iron Chelation Therapy on Gonadal Function in β-Thalassemia Major

Patients with transfusion-dependent thalassemia major tend to have abnormal growth and sexual maturation at puberty, presumably as a result of pituitary iron overload. This study was designed to determine whether chelation therapy with deferoxamine before the age of puberty would ameliorate this problem. We examined 40 patients over 14 years of age with transfusion-dependent thalassemia major. The 19 patients in group A (mean [+/- SD] age at study, 17.0 +/- 1.5 years) had begun nightly treatment with subcutaneous deferoxamine before the age of 10 (mean age at start of treatment, 7.5 +/- 1.8 years). The 21 patients in group B (mean age, 24.1 +/- 3.8 years) had begun treatment after the age of 10 (mean age at start of treatment, 14.4 +/- 4.7 years). The abnormal findings were essentially confined to sexual development. The final height did not differ between groups or from the mean parental height in each group. Ninety percent of the patients in group A had normal sexual development, as compared with 38 percent of those in group B (P = 0.001). Outcomes were correlated with indexes of iron overload; the patients in group A had lower serum ferritin levels before chelation treatment (P = 0.01) and lower average serum ferritin levels during treatment (P = 0.005). Beginning chelation treatment with deferoxamine before the age of puberty can help children with transfusion-dependent thalassemia major to attain normal sexual maturation.

The role of hormones in initiation of sexual maturation in male river lampreys ( Lampetra fluviatilis, L.): Gonadotropin and testosterone

Previous experiments with implantation of sex hormones indicated that development of increased sensitivity toward sex hormones in the peripheral tissues responsible for secondary sex characteristics is an essential feature in initiation of normal sexual maturation. The extent to which this sensitivity change depends on hormones from the pituitary gland was investigated by implanting testosterone pellets into 15 hypophysectomized (pro- and mesoadenohypophysis) immature male lampreys. Fin changes and growth of the urogenital papilla were elicited by testosterone in all hypophysectomized males, but were delayed in some in comparison with intact males. The testosterone-stimulated rate of growth of the urogenital papilla was slow in the hypophysectomized lampreys, but eventually normal size (8 mm) was reached. In untreated hypophysectomized lampreys the liver never turns green as it does in the majority of intact males, but testosterone induced green livers in 11 out of 14 hypophysectomized males. Thus it appears that the development in peripheral tissues of sensitivity toward sex hormones can take place without the presence of the pro- and mesoadenohypophysis. Furthermore, together with previous results obtained by hypophysectomy, the results support the idea that gonadotropin from the pro- and mesoadenohypophysis of lampreys is needed for the whole process of sexual maturation to occur, stimulates the rate of development, and allows simultaneous readiness for spawning in the population by especially stimulating slowly developing lampreys. On the basis of recent results and previous data it is suggested that the metaadenohypophysis and the interrenal cells also may be involved in initiation of sexual maturation.

Neuroendocrine mechanisms controlling the onset of female puberty

This article describes the major neuroendocrine developments that are associated with the normal onset of puberty in the female rats. Although differences exist between rats and humans with regard to development and function of the reproductive system, there are major basic similarities. This makes the rat a valuable laboratory model in which to evaluate the effects of potentially hazardous substances on normal sexual maturation. A systematic experimental approach is presented to show how the study of reproductive development in the female rat can aid our understanding of the processes by which these substances could disturb normal puberty in the human female.

Pituitary and gonadal function in hypogonadotrophic hypogonadal (hpg) mice bearing hypothalamic implants

GnRH receptor values are 30-50% of normal in pituitaries of hpg male mice, and testicular LH receptors only 8% of normal (160.4 +/- 17.6 and 2013 +/- 208.1 fmol/testis respectively). In male hpg mice bearing fetal preoptic area (POA) hypothalamic implants for 10 days there was no change in pituitary GnRH receptors, pituitary gonadotrophin content, or seminal vesicle weight. However, testicular weights and LH receptors were doubled in 4/10 mice and 2 had increased serum FSH levels. Between 26 and 40 days after implantation pituitary GnRH receptors and pituitary LH increased to normal male levels, although at 40 days serum and pituitary FSH concentrations had reached only 50% of normal values. Testicular and seminal vesicle weights increased more than 10-fold by 40 days after implantation and LH receptors to 70% of normal. In hpg female mice bearing hypothalamic implants for 30-256 days pituitary gonadotrophin concentrations were normal, even though GnRH receptors reached only 60% of normal values (6.18 +/- 0.4 and 9.8 +/- 0.4 fmol/pituitary respectively). Serum FSH was substantially increased from values of less than 30 ng/ml in hpg mice to within the normal female range in hypothalamic implant recipients. Ovarian and uterine weights increased after hypothalamic grafting from only 4-5% to over 74% of normal values. LH receptors increased from 6.5 +/- 1.3 fmol/ovary for hpg mice to 566.9 +/- 39.2 fmol/ovary for implant recipients. Vaginal opening occurred about 23 days after implantation and these animals displayed prolonged periods of oestrus.(ABSTRACT TRUNCATED AT 250 WORDS)

451 IMPAIRED PUBERTAL MATURATION IN BOYS FOLLOWING SUCCESSFUL THERAPY FOR TESTICULAR RELAPSE IN ALL

Four boys demonstrated variable delays in pubertal development following testicular irradiation(XRT) for biopsy proven testicular relapse(TR). The initial diagnosis of ALL was made by marrow aspirate and patients(pts) followed standard treatment (Rx) protocols. In 3 pts, the testis was the only site of relapse; the 4th had a concurrent CNS relapse. All pts are off Rx from 1 to 30 mos, having completed 2 additional yrs of systemic Rx and 24OO–2500 Rads XRT to both testicles. Three pts have elevated leutejnizing hormone (LH) and follicle stimulating hormone (FSH) reflecting testicular damage. Endocrine evaluations are as follows: CONCLUSIONS:1) After successful Rx for TR in ALL, hormonal response must be monitored throughniit puberty. 2)Supplementation with exogenous testosterone is likely to be needed in all cases. 3)Pts with TR after onset of puberty may have the best chance for normal growth and sexual maturation. 4)While sufficient Leydig cell function may be present to initiate pubertal development and increase testosterone above prepubertal levels, there does not appear to be adequate testosterone to complete virilization.

Normal sexual maturation and reproductive function in domestic hens following unilateral adrenalectomy

The ovulation-inducing properties of adrenal hormones and the anatomical juxtaposition of the left adrenal gland and the ovary suggest that a functional relationship exists between these two endocrine organs. To test this hypothesis, the effect of unilateral adrenalectomy on sexual maturation and reproductive function was examined in left and right adrenalectomized SCWL pullets. Between 9 and 13 weeks of age, 24 and 12 pullets were either left or right adrenalectomized, respectively; 12 birds were sham operated and 7 birds served as unoperated controls. Blood samples were obtained immediately before and after surgery, 48h after surgery and at 14, 19 and 23 weeks of age. All samples were analyzed for plasma corticosterone by radioimmunoassay. At 20 weeks of age all birds were weighed and the photoschedule was changed from 8L:16D to 16L:8D. During the first 52 days following photostimulation the age at first egg and the distribution of ovipositions within the 24h photoschedule were recorded. Mean plasma corticosterone levels of the unilaterally adrenalectomized hens were not significantly different (P > .05) from those of control birds 48h after surgery or at 14, 19 and 23 weeks of age. Unilateral adrenalectomy had no effect on body weight at 20 weeks, average age at first egg, or percent hen-day production. In addition, 95% of the eggs laid in the first 52 days after photostimulation were restricted to a 10 hour period of the day regardless of the surgical treatment. These observations indicate that the removal of either the left or the right adrenal gland does not affect plasma levels of corticosterone, sexual maturation, or the open period for LH release as evidenced by the times of oviposition and fail to support the hypothesis of a localized functional relationship between the left adrenal gland and the ovary.

Juvenile hormones (JHs) and completion of oöcyte development in the African migratory locust: A comparative and quantitative study

The effect of juvenile hormones (JHs) I and III on induction and completion of oöcyte development in allatectomized adult Locusta migratoria migratorioides females was studied. Whenever possible, oviposition rate served as a parameter, though, necessarily, oöcyte length was employed when no laying occurred. In the latter instance, oöcytes were usually measured twice, at laparotomy (special operation of the living female) and later at dissection. Normal (unoperated), allatectomized, allatectomized and later corpora allata (CA)-implanted females, as well as allatectomized females receiving solvents without hormone, constituted the controls. Allatectomy prevented oöcyte development, but reimplantation of CA led to its completion (laying). Injection or topical application of solvent(s) alone did not induce oöcyte development in allatectomized females. Topical application of JHI in methanol induced small, though distinct, vitellogenetic growth of the oöcytes. A more marked effect was obtained with JHI topically applied in olive oil. Injection of JHI greatly improved the effect, and only this method led to completion of oöcyte development. Hormone concentration in olive oil between 0.075 and 0.5% ( w v ), single or repeated (up to four) injections, did not influence oviposition rate for a 40-μg cumulative dose of JHI, though duration of laying was affected. Increasing cumulative doses of JHI, or JHIII, increased oviposition rate, furnishing well-defined dose-response curves. ED 50 (effective dose 50%, defined as 0.5 oviposition rate, that is, number of pods laid is equal to half the number of females) was about 30 μg per female for JHI and about 44 μg per female for JHIII. Thus, JHI was about 1.4–1.5 times more efficacious than JHIII. Ten micrograms of JHI did not induce completion of oöcyte development; 60 μg did so more than once in a portion of the females. Surprisingly, dosage and cumulative dose did not affect the number of eggs per pod, which always remained considerably lower than in normal (unoperated) controls. Pods laid by allatectomized and JH-injected females were viable, hatched reasonably, and the progeny achieved normal adult stage and sexual maturation. Injected JHI restored the secretory functioning of the oviduct. Unreliability of oöcyte length for assaying JH in adult female locusts, mode of JH administration, lack of difference in the results for single and repeated injections (of the same cumulative dose), and the crucial effect of the cumulative dose are discussed. Effective doses are considered as unphysiologically high, and some hypotheses are forwarded in explanation. The lack of effect of the cumulative dose on number of eggs per pod is also discussed and related to nutritional and/or metabolic factors, especially female-specific protein (=vitellogenin) synthesis.

Effects of prolactin on the sensitivity of the testis to LH.

Treatment of adult hypophysectomized rats with ectopic pituitary homografts caused a significant increase in testicular sensitivity to LH, as determined from measurements of peripheral testosterone levels 2.5 h after the injection of a single large dose of LH. Increased testicular responsiveness to acute LH stimulation was also observed after treatment with grafts or prolactin (PRL) combined with a chronic LH treatment, and in some instances, after treatment with PRL or chronic LH alone. It is suggested that PRL may have a role in sensitizing the testis to LH in the course of normal sexual maturation.

Endocrinology of puberty: I. Normal sexual maturation

The stages of sexual development in boys and girls are described and correlated with the changing hormonal secretory activities of the pituitary and gonads which accompany puberty. The roles of the hypothalamus and the central nervous system in the regulation of pituitary function during adolescence are described, and current hypotheses concerning the mechanisms by which puberty may be initiated are discussed.

Big Variability in "Little" People

The variegated community of dwarfs is proving to be more heterogeneous than generally thought. Monotropic sexual ateliotic dwarfism is a case in point. Distinguished from other pituitary dwarfs by their normal sexual maturation, individuals belonging in this category have a demonstrable isolated deficiency of immunoreactive growth hormone.¹Hitherto viewed as a homogeneous assemblage, they are now shown by Merimee and associates²to comprise several distinct groups sharply differentiated by hormonal and metabolic tests and sometimes by patterns of hereditary transmission. These investigators studied 26 American dwarfs and 31 African pygmies in whom they assayed growth hormone and insulin both before and after appropriate stimulation of secretion. They also assessed sensitivities to exogenous insulin as well as responses to growth hormone therapy; and, when possible, they determined modes of inheritance. From these studies have emerged distinct patterns of values and responses to justify the subdivision of monotropic ateliotic sexual

A METABOLIC AND HORMONAL BASIS FOR CLASSIFYING ATELIOTIC DWARFS

Four distinct types of sexual ateliotics with short stature and normal sexual maturation can be detected by immunoassay of growth hormone (H.G.H.) and insulin, and by metabolic tests. In group I, H.G.H. is not present in plasma after provocative stimuli; there is prolonged hypoglycæmia after insulin, and insulinopenia after arginine and glucose; all respond to H.G.H. In group II, H.G.H. is again not detectable, and hyperinsulinism (not insulinopenia) is seen after glucose and arginine, this group is resistant to exogenous insulin and to H.G.H. In group III, the basal plasma-H.G.H. is abnormally elevated and not suppressed by hyperglycæmia, individuals are similar to those in group I except for decreased responsiveness to H.G.H. In group IV, the H.G.H. response in tests is normal; individuals in this group are similar to those in group I, but are completely unresponsive to exogenous H.G.H. The type of dwarfism and the potential usefulness of H.G.H. therapy cannot be predicated on the simple absence or presence of H.G.H.

Hypophyseal functions in river lampreys

Two main problems have been investigated: (1) the importance of the pituitary gland for normal sexual maturation; (2) the importance of normal contact between the central nervous system and the pituitary gland for its gonadotropic function. The river lampreys of northern Europe migrate from sea to the rivers in autumn. They then stop feeding and mobilize body tissues, mainly the body wall, to cover energy requirements and make possible the growth of gonads. In late winter or spring secondary sexual characters develop and the animals spawn. An increased mobilization of body tissues, an increased level of blood sugar, an accelerated spermatogenesis, and an increased growth of ovaries was demonstrated in this period of development. Shortly after spawning the animals die. Extirpation of the pro- and mesoadenohypophysis was performed before and during sexual maturation. Lampreys operated upon before sexual maturation continued the slow mobilization of body tissues and the slow growth or differentiation of gonads. Their blood sugar concentration was like that of normal animals before sexual maturation. They developed no secondary sexual characters, and no release of gonadal products to the body cavity took place. In lampreys which survived operation during sexual maturation, the mobilization of body tissue slowed down. In males, the growth of the urogenital papilla stopped and the fin alterations and cloacal swelling regressed, whereas release of sperm did take place in the absence of the pituitary gland. The secondary sexual characters of female lampreys operated upon during sexual maturation developed a little further and then development stopped; ovulation did seldom take place. Extirpation of the pro- and mesoadenohypophysis prolongs the survival of the lampreys; it is suggested that natural death may be caused by depletion of body tissue mainly. Transplantation experiments show that pro- and mesoadenohypophyseal tissue deprived of its normal connection with the central nervous system may secrete gonadotropin. That part of the pro- and mesoadenohypophysis which could be removed in one piece was transplanted to a muscle in the pharynx. The remaining pro- and mesoadenohypophyseal tissue was sucked out. As a control, a similar piece of pro- and mesoadenohypophysis was replaced in its normal position after removal of remnants. Transplants placed in the muscle permitted sexual maturation in 4 out of 8 males. Pro- and mesoadenohypophyseal tissue replaced in its normal position permitted sexual maturation in 4 out of 6 males.

Spontaneous Sexual Development in a Chromatin Negative Female with XO Blood Leukocyte Karyotype

Although Turner's syndrome is usually associated with a spectrum of phenotypic abnormalities, the relatively constant features are short stature and the absence of breast development, menstruation, and fertility. An unusual exception to this general prognosis was the case reported by Bahner, et al.1,2 Their patient had short stature and a low occipital hairline; she was chromatin negative and karyotypically XO in cultures of bone marrow, skin, and both ovaries. She showed normal sexual maturation and at age 31 years delivered a normal male infant. The present report describes a chromatin negative patient who exhibited spontaneous breast development at age 12 years. This prompted a histologic and chromosomal investigation, the results of which are discussed below.

Effect of Removal of the Frontal Ganglion on Corpus Allatum Function in Locusta migratoria migratorioides R. & F.

REMOVAL of the frontal ganglion from young adults of Locusta migratoria L. prevents normal growth and sexual maturation; the operation is thought to interfere with the activity of the cerebral neurosecretory system1. It is possible, however, that the removal of the frontal ganglion affects the activity of the corpora allata which are also essential for maturation in locusts2,3. This possibility has been investigated using adults of Locusta migratoria migratorioides R. & F.

MENSTRUAL DISORDERS OF ADOLESCENCE.

Adolescent menstrual disorders include precocious puberty, delayed menarche, dysfunctional uterine bleeding, and dysmenorrhea. The menarche normally takes place between the ages of 9 and 16 years. Precocious puberty of constitutional origin, by far the most common variety, is characterized by accelerated but otherwise normal sexual maturation. Recognition of delayed maturity hinges on other evidence of “lateness” and on absence of endocrine stigmas. Early in adolescence the menstrual cycles are often bizarre by adult standards. Progesterone is the mainstay of therapy for abnormal uterine bleeding in adolescence. Dysmenorrhea deserves special attention because it engenders fears of marital or reproductive disaster.