The role of the limbic forebrain structures in controlling twice daily surges of prolactin (PRL) induced by cervical stimulation was investigated after acute or chronic deafferentation of the limbic forebrain afferents to the hypothalamus in rats. The preoptic area-roof section (POA-RS), which interrupted the rostral limbic afferents at the dorsal level of the anterior commissure, induced pseudopregnancy (PSP) and initiated the same nocturnal PRL surges as those initiated by the cervical stimulation. Diurnal PRL surges, however, did not occur following this procedure. The nocturnal PRL surge by POA-RS also occurred in ovariectomized rats. Deafferentation between the diagonal band of Broca and the medial preoptic area (F₂-cut) initiated PSP in 37 % of the rats and induced an apparent but small nocturnal PRL surge. The rats with POA-RS or F₂-cut showed restoration of their regular estrous cyclicities. Cervical stimulation after POA-RS did not affect the initiation of nocturnal PRL surge induced by POA-RS alone. POA-RS after cervical stimulation also did not affect the initiation of nocturnal PRL surge induced by cervical stimulation, though a diurnal PRL surge was initiated in these rats. The cut made just before the diagonal band of Broca after cervical stimulation did not inhibit the occurrence of either surge. Nocturnal and diurnal PRL surges were manifested after cervical stimulation in the rats with chronic POA-RS or F2-cut and their vaginal cyclicities were resumed. These results suggest that the limbic forebrain structures are not indispensable for the initiation of nocturnal PRL surges induced by cervical stimulation but may modify the hypothalamic mechanism (s) initiating a nocturnal PRL surge through the rostral part of the hypothalamus.

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The volume of the ventromedial nucleus of the hypothalamus (VMN) of normal male rats was significantly greater than that of normal female rats. Castrationof day 1 neonatal males significantly reduced the volume of the VMN to a level comparable with that of normal females. However, the VMN volume was no longer influenced by castration on day 7. Injection of 1.25mg testosterone propionate to 5-or 15-dayold females did not have any significant effect on the volume of the VMN. These results indicate that the volume of the VMN is sexually dimorphic and is modified by internal secretion of neonatal testes.

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Intracranial actions of estradial benzoate (EB) in modulating the characteristics pulsatile LH secretion were examined in ovariectomized rats. A minute amount crystalline EB was implanted into the medial basal hypothalamus (MBH) or the preoptic suprachiasmatic area (POSC) and blood samples were collected at 6-min intervals for radioimmunoassay of serum LH concentrations. In rats with EB implanted in. the MBH, the LH pulse amplitude decreased while the frequency did not change for 3 h after implantation. In rats bearing EB implants in the POSC, in contrast, the LH pulse frequency decreased without a significant variation in the pulse amplitude. Control animals with empty cannulae inserted into the MBH or POSC exhibited unchanged amplitude and frequency of LH secretory pulses. These results indicate that estrogen can regulate the amplitude and frequency of pulsatile LH secretion via mechanisms independent of each other. It appears that MBH and/or the pituitary is a site of the action of estrogen in decreasing LH pulse amplitude, while the POSC is a site of the steroid action in decreasing the pulse frequency.

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The isoelectric components of LH have been isolated from the male rat pituitary glands by preparative isoelectric focusing. The biological activities of thesecomponents were measured in vitro from testosterone production in rat Leydig cells at equal doses and expressed as the equivalent of NIH-LH-Sl immunoreactivity. There were significant differences in the bioactivities among the components. The bioactivities of the components decreased with decreasing pI; components E (pI=9.6) and F (pI=9.8) showed about 5-to 6-fold higher activities than component A'(PI=7.9). When the rat pituitary extracts were measured for LH by radioimmunoassay, and then measured for the ratio of biological activity to immunoreactivity (B: I), theorder was as follows; intact female rats>intact male rats>orchidectomized rats. This phenomenon could be explained by the differences in the relative amounts of the LH components which changed according to the physiological states. These observations indicate that the LH components with different pis and B: I ratio are related to the different estimation of total LH in the rat pituitary glands by bioassay and radioimmunoassay.

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The detailed profile of prolactin (PRL) secretion in 22-24 and 29-31 days old female rats was investigated by serial blood sampling through an intracardiac cannula at 15-min intervals for each of the 9 or 10-h periods beginning at 09.00 or 10.00 and 22.00 h. By analysis of the power spectrum and the least squares method the time series of PRL concentrations which were measured by RIA were found to have approximately a 3-h period ultradian rhythm in either sampling period of both the 22-24 and 29-31 days old rats. The peak times calculated based on the acrophase estimated through the calculation of periodicity were concentrated around 12.00, 15.00 and 18.00 h for the sampling period 10.00-19.00, and 24.00, 03.00 and 06.00 hfor the sampling period 22.00-07.00 h. However, in more than half of the animals at 22-24 days of age, one secretory episode around 12.00 h, and two secretory episodes around 24.00 and 03.00 h had markedly small amplitudes, making the remaining secretory episodes distinct diurnal and nocturnal surges, respectively. In the animals at 29-31 days of age, the amplitudes of the PRL episodes occuring around 12.00 hwere markedly small, making the remaining to episodes as diurnal surges, whereas the amplitudes of PRL secretory episodes during the period 22.00-07.00 h were analogous to each other. These findings indicate that the semicircadian rhythm of PRL secretion is established on the basis of PRL secretion with the 3. 0-h period ultradian rhythm.

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The effect of implantation of cholecystokinin (CCK)-8 into the medial preoptic area (MPO) through the chronically implanted guide cannula on the release of LH was examined in the ovariectomized estradial-primed rat. An inner cannula with CCK-8 at the tip, as well as an empty inner cannula as the control, was implanted into the MPO at 12.00 h. Blood samples were obtained at 11.00, 12.00, 16.00, 18.00 and 20.00 h, and serum concentration of LH was measured by RIA. There was no significant fluctuation over time in the mean serum LH values for each sampling time in the group of animals implanted with empty cannulae in the MPO. In the group of animals implanted with CCK-8 into the MPO, the fluctuation of the mean LH values over time was significant, with a marked and significant elevation of LH values peaking at 16.00 h.
It was strongly suggested that CCK-8 was capable of stimulating LH-RH release, acting at the MPO.

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The effect of γ-aminobutyric acid (GABA) on antidromically identified tuberoinfundibular (TI) neurons was examined in hypothalamic slices of ovariectomized female rats. Twenty antidromically evoked spikes were obtained in the medial basal hypothalamus, including the arcuate and ventromedial nuclei, by electrical stimulation the median eminence. Sixteen of them had a notch in the rising phase and fractionation of the initial segment (IS)-and somatodendritic (SD)-spikes was elicited by repeated stimulation at frequencies higher than 10Hz. The application of 0.5-1.5mM GABA to the incubation medium inhibited SD spikes in 7 of these 16 neurons. The latency, amplitude and threshold of IS spikes were not affected by GABA except for one spike whose latency fluctuated. On the remaining 9 neurons having the notch, effect of 5-10 mM GABA was discernible. Four of 20 antidromically evoked spikes, which had a smooth rising phase and a shorter duration, were notinhibited 5-10 mM GABA, but a fluctuation of the latency was observed in one neuron.
Fifteen neurons having spontaneous unit activity were also obtained in the arcuate nucleus and its adjacent area and tested with GABA. In 10 of the 15 neurons, spontaneous unit activity disappeared following 0.1-1.5 mM GABA perfusion, while the firing rate in the remaining 5 neurons was not affected by 5-10 mM GABA.
These results provide evidence for a direct inhibitory effect of GABA on TIneurons and support the involvement of GABAergic neurons in regulating neuroendocrine functions.

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The effect of spinal transections on the preovulatory release of gonadotropins and PRL was investigated in female rats. A preovulatory rise in serum LH, FSH and PRL and subsequent ovulation were prevented by complete spinal transections (CST) at high thoracic levels (T3-T7), but not at low thoracic and lumbar levels (T8-L5), performed at 1000-1230 h on proestrus. Norepinephrine (NE) concentrations in the preoptic-anterior hypothalamic area at 1700-1800 h on proestrus were also significantly reduced by CST at high thoracic levels, but not at lumbar levels. Either electrochemical stimulation of the suprachiasmatic part of the preoptic area or NE injection into the third ventricle at 1400-1500 h on proestrus restored ovulation in animals with CST at high thoracic levels. Animals with CST at lumbar levels exhibited relatively regular 4-day cycles, but those with CST at high thoracic levels showed prolonged periods of diestrous (8-20 days) before they resumed cyclicity.
In the case of partial transections, bilateral transections of the lateral columns, but not transections of the dorsal or medial columns, of the spinal cord at T4-T5 significantly blocked the preovulatory gonadotropin release and the occurrence of ovulation. Unilateral transections of the lateral columns of the spinal cord or unilateral electrolytic lesions of the ventrolateral part of the medulla oblongata (VLMO) failed to block ovulation. When combinations of them were performed ipsilaterally, ovulation occurred, but when they were performed contralaterally, the incidence of ovulation was significantly decreased.
These results suggest that the ascending neural pathway in the lateral columns of the spinal cord projecting to the ipsilateral VLMO participates in the neural mechanisms controlling the preovulatory release of gonadotropins and PRL by maintaining NE levels in the preoptic-anterior hypothalamic area.

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A 17-year-old boy with pituitary gigantism who had two episodes of diabetic ketoacidosis is reported. Glucose tolerance and insulin secretion were evaluated before, during and after each episode of ketoacidosis. The patient was 201 cm tall and weighed 137 kg. Before surgery, his plasma growth hormone level was 3, 000 ng/ml, glucose tolerance was almost normal and insulin response to glucose load was enhanced. He fell into diabetic ketoacidosis twice; 3 weeks after hypophysectomy and one year later after getting the “flu”. On each occasion, insulin treatment was needed only temporarily. After the ketoacidosis improved, glucose tolerance and C-peptide responses became nearly normal. Urine C-peptide was low during and immediately after the second episode, but increased to normal following recovery. It is presumed that a pre-operative compensation for the diabetogenic action of excess growth hormone by hyper-secretion of insulin was broken when superimposed stress was added. This is an example in which subnormal insulin response may not be a prerequisite for the occurrence of a severe diabetic state, and decompensated insulin secretion leading to ketoacidosis may not imply permanent damage to the beta cells.

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The role of a “steroidogenic factor” in the corticoidogenic response to adrenocorticotropic hormone (ACTH) was studied in this experiment. ACTH caused an accumulation of cholesterol within the adrenocortical mitochondria in rat after pretreatment with either cycloheximide (CH) or aminoglutethimide (AG). The cholesterol distribution in these cholesterol-rich mitochondria was examined by measuring the cholesterol concentrations in the outer and inner mitochondrial membranes. In the case of pretreatment with CH, cholesterol was accumulated in the outer membrane and not in the inner membrane. In contrast, in the case of pretreatment with AG, cholesterol was accumulated in the inner membrane and not in the outer membrane.
It could be concluded from the presented data that the function of a “steroidogenic factor” in the corticoidogenic response to ACTH might take place at the step of cholesterol translocation from the outer mitochondrial membrane to the inner membrane.

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To examine the relationship between the sleep rhythm and the gonadal feedback system in the guinea pig, the effects of estrous cycle, gonadal steroids and brain deaf-ferentations on the sleep rhythm were studied and the following results were obtained;1) the guinea pigs did not show an apparent circadian rhythmicity in the sleep-wake-fulness cycle but showed an ultradian rhythm, whereas, the activity rhythm was circadian, 2) the rhythm in paradoxical sleep (PS) showed changes associated with the estrous cycle which were characterized by a decrease and rebound-like increase in PS amounts on the day of proestrus, 3) the horizontal deafferentation above the medial preoptic area at the level of the anterior commissure (MPO roof cut) did not disrupt the estrous cycle dependent changes in the PS rhythm, but the prechiasmatic deafferentation of the medial basal hypothalamus (PCD) and the large complete deafferentation of the medial basal hypothalamus (CDL) disrupted them, 4) ovariectomy (OVX) did not result in any changes in sleep and activity rhythms, 5) an administration of estradiol benzoate (E2) to OVX guinea pig caused a decrease in the amount of PS and an administration of progesterone (P) 48 h after E 2 caused a more pronounced decrease and rebound-like increase in the amount of PS, 6) the MPO roof cut did not affect the steroidal modification of the PS rhythm and the PCD disrupted it, while the CDL-animal also showed a E 2-induced PS decrease.
From these results, it appears that the guinea pig may be a circadian animal, but this may not be seen in the sleep-wakefulness cycle, and the estrous cycle dependent changes in the PS rhythm may be the reflection of steroidal modification of the sleep rhythm and the site of action may be the inside of the medial preoptic anterior hypothalamic structures, but this area may also be affected by the output from the medial basal hypothalamus.

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The secretory profile of prolactin and oxytocin in response to sucklin stimuliby litters was studied in unanesthetized and urethane-anesthetized lactatin rats. Serum prolactin levels were determined by radioimmunoassay. Oxytocin released at milk-ejection reflex was monitored by the changes in the intramammary pressure and/or the characteristic pup's reaction associated with the milk ejection. Serum prolactin concentrations began to rise earlier than the first milk ejection in unanesthetized rats, but they were never elevated without the appearance of milk ejections in urethane-anesthetized rats. Pulsatile fluctuation in serum prolactin levels at 6-15 min intervals was observed in the nursing period when 10 pups were suckling continually. The intermittent milk-ejection reflex occurred not always but preponderantly (64-91%) when the serum prolactin levels were at the nadir of the fluctuation Injection of an estimated dose of oxytocin released at each milk ejection (1 mU) did not change the serum prolactin levels. These results indicate that the mechanism for prolactin release may be more susceptible to the effects of anesthesia than that for oxytocin release in response to the suckling stimuli and that the release of both the hormones is pulsatile in nature and be influenced by a common biological clock during the nursing period.

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The effect of an increase in plasma osmolality on the milk-ejection reflex of rats was studied. The lactating rats, at day 8-12 of lactation, were anesthetized with urethane (1.1 g/kg, i. p.) and 8-11 pups which had been separated from their mother 16-18 h were put to the nipples to suckle. In 21 of 47 rats studied an intermittent pattern of milk ejection was recorded with a latency of 15-74 min (group-I rats). The mean interval between recurring milk ejections was 8.3±0.6 (S.E.M.) min and the mean amount of oxytocin released at each milk ejection estimated in 11 of them was 0.26±0.04 mU. The remaining 26 rats showed no milk ejection throughout the nursing period of more than 90 min (group-II rats).
The intraperitoneal injection of 1.5 M NaCl (1 ml) had no effect on the interval between milk ejections but increased the amount of oxytocin released at each milk ejection by 2.4 times in group-I rats, as the plasma osmolality changed from 297.9±2.7 mOsm/kg to 310.4±3.6 mOsm/kg. On the other hand, the 1.5 M NaCl injection induced recurring reflex milk-ejections in all of the group-II rats, while the plasma osmolality increased from 307±2.8 mOsm/kg to 320±3.1 mOsm/kg. The mean interval was not significantly different from that observed in the group-I rats. The sensitivity of the mammary gland to oxytocin was not altered by the 1.5 M NaCl injection. The injection of isotonic NaCl had no effect on the milk-ejection reflex.
These results indicate that an increase in plasma osmolality facilitates the milk ejection reflex in rats by increasing the amplitude but not by changing the rhythmicity.

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17β-Hydroxysteroid oxidoreductase in the human testis was investigated histochemically using tissues obtained from seven patients with undescended testis or varicocele at the time of orchiopexy or high ligation of spermatic vein. Formazan precipitates were formed from nitro-blue tetrasolium in the tissue utilizing hydrogen released by oxidation of testosterone, which is catalized by the reductase function of 17β-hydroxysteroid oxidoreductase. The precipitates were formed specifically in the presence of 17β-hydroxy-C₁₉-steroids under the conditions employed in the present study. In infantile testes, the precipitates were formed in cytoplasm of immature Sertoli cells, while in pubertal or adult testes, marked formazan precipitates were found in cytoplasm of both Sertoli and Leydig cells. The results indicate the presence of two distinct 17β-hydroxysteroid oxidoreductases in the human testis; one in Sertoli cells and detectable independent of age and the other only in functional Leydig cells.

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We examined the responses of serum free C-peptide immunoreactivity (CPR) during a 100g oral glucose tolerance test (OGTT) on diabetic patients undergoing different kinds and durations of treatment. None of the patients were ketosis-prone or had any history of nephropathy and they all developed diabetes when over the age of 30. The Σ serum free CPR (the sum of serum free CPR values during OGTT) of group A (duration of insulin treatment was less than 5 years, N=10) was found to be higher than that of group B (duration of insulin treatment was 5 years or more, N =10)(p<0.005). On the other hand, the Σ serum free CPR of group C (treatment with an oral hypoglycemic agent for less than 5 years, N=9) was not statistically different from that of group D (treatment with an oral hypoglycemic agent for 5 years or more, N=11). There were no statistical differences between group A and group B in age at onset, duration of diabetes, daily insulin dose, relative body weight index, serum creatinine or ΣBG (the sum of blood glucose values during OGTT). Just before the start of insulin treatment, there were no significant differences between the two groups in the following: 1. fasting blood glucose values (all 10 patients measured in group A and 9 patients in group B) 2. blood glucose and plasma immunoreactive insulin (IRI) responses (7 patients measured in group A and 6 in group B). Among those with plasma IRI measured on the previous occasion, Σserum free CPR was found to be higher in group A than in group B (p<0.025) at the time of the present study. A negative correlation was noted between the duration of insulin treatment and Σserum free CPR in insulin-treated patients (r=-0.39, p<0.05). Thus, pancreatic B-cell function in insulin-treated noninsulin-dependent diabetic patients is likely to be inversely correlated with the duration of insulin treatment.

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Pseudopregnancy (psp) can be induced by a single injection of progesterone in cyclic rats and the administration of anti-progesterone serum can block the establishment of psp in cervically stimulated rats. To further investigate neuroendocrine mechanisms for the initiation of either psp or prolactin (PRL) surges in connection with the neurotropic action of progesterone, cytosolic progestin receptors (PRc) were identified and measured in preoptic (POA) and basal hypothalmic (BH) areas.
Chronological determinations of PRc concentrations in both areas revealed large fluctuations in the morning of the estrous day but not in the morning of the diestrous day. The di fferences between the maximal and the minimal PRc concentrations observed were more than 100-fold in POA and 3-fold in BH. Cervical stimulation applied in the afternoon of the proestrous day significantly altered the changing pattern of PRc concentrations in POA but not in BH. One of the two peaks of PRc concentrations in POA was magnified and advanced earlier to 0300 h, and then the 1st PRL surge peaking at 0700 h occurred. This PRL release seemed to stimulate progesterone secretion and an elevation of peripheral progesterone levels coincided with the 2nd peak of PRc concentrations in POA at 0900 h. This coincidence may be a prerequisite for the further continuation of PRL surges.
These results strongly suggest that the spontaneous oscillation of the PRc concentration in hypothalamic neurons is involved in the regulation of PRL secretion and that cervical stimulation shifts the phase and changes the amplitude.

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Freshly obtained human placentas from various periods of gestation were quantitatively analysed for their immunoreactive oxytocin (OT) content and its biological activity was examined in a Magnus apparatus by utilizing rat uterus.
The mean values for placental immunoreactive OT per gram tissue increased from the first to the second trimester, maintaining its high level to term. The total content of placental OT also increased continually from the beginning of pregnancy to term. Blood levels of estrogen stimulated neurophysin (ESN) and OT were concomitantly enhanced through gestation. Placental extract and synthetic OT showed similar peaks in the elution pattern of ion-exchange chromatography through a carboxymethyl cellulose column. Synthetic OT and placental extract induced marked uterine contraction in diestrous rats. However placental extract previously incubated with OT antiserum failed to induce this effect.
Though detection of immunoreactive OT by immunoassay alone does not provide definite identification of pituitary and placental OT, the present study suggests that placental immunoreactive OT could have a contracting effect on the uterine muscle.

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To determine the localization of the clonidine sensitive area responsible for GH release, a minute amount of the α₂-agonist (67ng/0.2μl) was injected into the hypothalamus and vicinity of adult male concious rats. The animals were chronically implanted with double metal cannulae fixed on the skull for clonidine microinjection and with silastic tubing into the right atria for collecting blood samples. Ten hr prior to the microinjection, α-methyl-p-tyrosine (250mg/kg body weight) was intraperitoneally injected to prevent spontaneous pulsatile GH release. Localization of the microinjection was assessed by histological examination after the experiment. Clonidine microinjection into the amygdala nucleus had no effect on GH release, while the injection into the preoptic and anterior hypothalamic area (PO/AH) significantly stimulated GH release by causing it to begin 30 min earlier. However, the paraventricular nucleus, the dorsomedial nucleus, the lateral hypothalamus and the ventromedial hypothalamus areas did not respond to the injection, although the latter nucleus has been shown to be a specific locus sensitive to electrical stimulation of release. In the area from the posterior hypothalamus to the mammillary body, several injections stimulated GH release (6/15), but the stimulatory effect was statistically insignificant when comparison was made with the mean (±SE) for all 15 rats.
These findings suggest that the α₂-agonist acts on the PO/AH to induce an increase in GH release in α-methyl-p-tyrosine-pretreated rats, probably mediating the inhibitory input to somatostatinergic neurons which reside in the periventricular nucleus of the PO/AH area.

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Previously we have found that small lesions confined to the medial preoptic nucleus (MPN) or the suprachiasmatic nucleus (SCN) blocked the cyclic release of gonadotropins in the female rat, inducing a persistent estrous state. Since the MPN is located just caudal to the organum vasculosum of the lamina terminalis (OVLT) where LHRH cell bodies are most concentrated, we applied an immunocytochemical technique to examine the possibility that the lesions had simply disrupted LHRH neurons or fibers.
Using a new anti-LHRH provided by Dr. V. D. Ramirez, we found that the distribution pattern of immunoreactive LHRH cell bodies and fibers was similar to that previously reported, although the staining was more intense and extensive with low background. There was no concentration of LHRH cell bodies and fibers in the MPN or SCN and, in fact, these nuclei generally showed a lower density of stained elements than did sorrounding tissue. In persistent estrous animals with lesions confined to the MPN there was no detectable reduction of staind fibers in the median eminence.
These results, along with the results of other workers, suggest that persistent estrus following lesions of the MPN or SCN is not due to reduction of LHRH neurons or fibers. Rather, they support the hypothesis that these nuclei are critical for triggering the ovulatory release of LHRH.

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The effects of third ventricular injection of β-endorphin (β-EP) on spontaneous, brain stimulation-induced and estrogen-induced LH surges were studied in the adult female rat. It was found that β-EP blocked the preovulatory surge of LH release and ovulation, while it did not affect LH release in response to LH-RH injection. The site of the β-EP blockade of ovulation was proved to be in the brain. Beta-EP completely blocked ovulatory LH release induced by the electrochemical stimulation of the medial amygdaloid nucleus and medial septum-diagonal band of Broca, but failed to block ovulation due to the stimulation of the medial preoptic area (MPO) or median eminence, though serum LH levels after the MPO stimulation were inhibited by β-EP. In the spayed rats treated with estradiol benzoate (EB) on Day 1 and 4 of experiment, β-EP given on Day 5 blocked the LH surge that normally occurred on that day and led to a compensatory surge of LH on the following day. Moreover, the LH surge on Day 5 was inhibited by β-EP given either on Day 1 or Day 4. Present data suggest that β-EP may act in inhibiting the preovulatoy LH surges not only by suppressing the preoptic-tuberal LH-RH activities but also by affecting the initiation and development of stimulatory feedback of estrogen in the central nervous system.

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The development of estrogen feedback system ongonadotropin release during sexual maturation in female rats was studied. Animals (Wistar strain rats) were divided into 6groups according to their ages; 10, 15, 20, 25, 30, and 35 days. Both LH and FSH levels in serum increased significantly in response to ovariectomy in all age-groups studied when measured one week postoperatively, though in the rats aged 10-15 days the increase in FSH following castration was only slight. In rats older than 25 days, the postcastrationgonadotropin rise, calculated as a percent increase from the basal figure, decreasedgradually with increasing age. Ovariectomized rats injected with estradiol benzoate (EB, 5 μg/100g BW) showed significantly lower levels of both LH and FSH than those in castrated controls. However, the inhibitory action of EB on postcastrationgonadotropin output was found to be relatively less effective in rats older than 25 days.
Ovariectomized rats primed with EB were again injected with a 2nd dose of EB (5 μg/100g BW) at noon 3 days after priming. The 2nd EB injection induced a significant rise in LH 6 h later in 30-and 35-day-old, though not in younger, animals. On the other hand, the FSH response to EB was markedly enhanced during days 15-25 of age. These results indicate that the estrogen negative feedback action on gonadotropin release is already operating in female rats at a very early age, and that the brain sensitivity to estrogen decreases slightly during the late prepubertal phase. In addition, the stimulatory effect of estrogen on LH release fully develops shortly before the onset of puberty, whereas the stimulatory estrogen control of FSH is initiated around the 2nd week of postnatal life.

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